J. Krušek - Academia.edu (original) (raw)

Papers by J. Krušek

Research paper thumbnail of Potassium buffering by Müller cells isolated from the center and periphery of the frog retina

Glia, 1999

Müller (radial glial) cells span the retina from the outer to the inner limiting membranes. They ... more Müller (radial glial) cells span the retina from the outer to the inner limiting membranes. They are the only glial cells found in the amphibian retina. The thickness of the frog (Rana pipiens) retina decreases by a factor of about four from the center to the periphery. Thus, Müller cells were isolated, by enzymatic dissociation, with stalk lengths from 20 to 140 microm. Their ability to transfer K(+) via the stalk between soma and endfoot was studied. Membrane currents were recorded using the whole-cell voltage-clamp technique with the pipette sealed to either the endfoot or the soma. Inward (I(KIN)) or outward (I(KO)) currents were elicited by rapid increases (3 to 10 mM) or decreases (3 to 1 mM) of the extracellular K(+) concentration ([K(+)](o)) either by local application (close or distant to the recording pipette) or around the entire cell (whole cell perfusion). For the long central cells, the ratio I(KIN)/I(KO) was 4.6 +/- 0.6 SE (n = 9) at the endfoot and 1.7 +/- 0.1 SE (n = 8) at the soma. In cells from the retinal periphery, the ratio I(KIN)/I(KO) was higher, 7.0 +/- 0.27 (n = 8) at the endfoot and 3.2 +/- 0.1 (n = 10) at the soma. The results suggest that there is less inward rectification in the somatic than in the endfoot membrane. As expected from previous studies, the sensitivity of the cells to K(+) was higher at the endfoot than at the soma. The amplitude of I(KIN) at the endfoot compared to the soma was about 8-fold for the long central cells but only about 1.5-fold for the short peripheral cells. Currents spread readily from endfoot to soma in the peripheral cells. In the long central Müller cells the soma and endfoot appeared electrotonically isolated. The "functional length constant", lambda, of cell stalk processes was about 70 microm. The relative decrement of large inward currents was stronger than that of smaller outward currents; this difference ("artificial rectification") is explained by a simple model, where larger currents (inward) are attenuated more than smaller (outward) currents. The data support the hypothesis that in the retinal periphery, Müller cells provide extensive spatial K(+) buffering from both plexiform layers into the vitreous body. In the central retina, however, such currents are limited within a short (interlaminar) range.

Research paper thumbnail of Spatial distribution of spermine/spermidine content and K+-current rectification in frog retinal glial (M�ller) cells

Glia, 2000

Previous studies in retinal glial (Mü ller) cells have suggested that (1) the dominant membrane c... more Previous studies in retinal glial (Mü ller) cells have suggested that (1) the dominant membrane currents are mediated by K ϩ inward-rectifier (Kir) channels (Newman and Reichenbach, Trends Neurosci 19:307-312, 1996), and (2) rectification of these Kir channels is due largely to a block of outward currents by endogenous polyamines such as spermine/spermidine (SPM/SPD) (Lopatin et al., Nature 372:366-369, 1994). In frog Mü ller cells, the degree of rectification of Kir-mediated currents is significantly higher in the endfoot than in the somatic membrane (Skatchkov et al., Glia 27:171-181, 1999). This article shows that in these cells there is a topographical correlation between the local cytoplasmic SPM/SPD immunoreactivity and the ratio of inward to outward K ϩ currents through the surrounding membrane area. Throughout the retina, Mü ller cell endfeet display a high SPM/SPD immunolabel (assessed by densitometry) and a large inward rectification of K ϩ currents, as measured by the ratio of inward to outward current produced by step changes in [K ϩ ] o. In the retinal periphery, Mü ller cell somata are characterized by roughly one-half of the SPM/SPD immunoreactivity and K ϩ-current rectification as the corresponding endfeet. In the retinal center, Mü ller cell somata are virtually devoid of both SPM/SPD immunolabel and K ϩ-current inward rectification. Comparing one region of the retina with another, we find an exponential correlation between the local K ϩ rectification and the local SPM/SPD content. This finding suggests that the degree of inward rectification in a given membrane area is determined by the local cytoplasmic polyamine concentration. GLIA 31:84-90, 2000.

Research paper thumbnail of The pharmacology of tacrine at N-methyl-d-aspartate receptors

Progress in neuro-psychopharmacology & biological psychiatry, Apr 3, 2017

The mechanism of tacrine as a precognitive drug has been considered to be complex and not fully u... more The mechanism of tacrine as a precognitive drug has been considered to be complex and not fully understood. It has been reported to involve a wide spectrum of targets involving cholinergic, gabaergic, nitrinergic and glutamatergic pathways. Here, we review the effect of tacrine and its derivatives on the NMDA receptors (NMDAR) with a focus on the mechanism of action and biological consequences related to the Alzheimer's disease treatment. Our findings indicate that effect of tacrine on glutamatergic neurons is both direct and indirect. Direct NMDAR antagonistic effect is often reported by in vitro studies; however, it is achieved by high tacrine concentrations which are not likely to occur under clinical conditions. The impact on memory and behavioral testing can be ascribed to indirect effects of tacrine caused by influencing the NMDAR-mediated currents via M1 receptor activation, which leads to inhibition of Ca(2+)-activated potassium channels. Such inhibition prevents membran...

Research paper thumbnail of Overexpression of the G protein G11α prevents desensitization of CA2+ response to thyrotropin-releasing hormone

Life Sciences, 1999

Doubly transfected human embryonal kidney cells (clone E2M11 of the HEK 293 cell line) expressing... more Doubly transfected human embryonal kidney cells (clone E2M11 of the HEK 293 cell line) expressing both thyrotropin-releasing hormone (TRH) receptors and Gll a protein in high amounts were used to analyze the desensitization phenomenon of the Ca"-mobiiig pathway. Quite unexpectedly, we did not observe any significant desensitization of the [Ca2']i response to TRH in these cells after repeated or prolonged incubation with the hormone (up to 5 h). Under the same conditions, the TRH-induced [Ca"]i response was completely desensitized in the parent cell line (293-E2 eels) expressing TRH receptors alone. In both cell lines, inositol phosphate response was desensitized after TRH exposure, although basal levels of inositol phospates in TRH-pretreated cells were much higher than in "naive" TRH-unexposed cells. These data suggest a significant role of the G protein GIla in desensitization of the Ca2'-mobilizing pathway occuring after repeated or long-term exposure of target cells to TRH-receptor agonists.

Research paper thumbnail of Ca2+ responses to thyrotropin-releasing hormone and angiotensin II: the role of plasma membrane integrity and effect of G11α protein overexpression on homologous and heterologous desensitization

Cell Biochemistry and Function, 2008

The molecular mechanisms involved in GPCR-initiated signaling cascades where the two receptors sh... more The molecular mechanisms involved in GPCR-initiated signaling cascades where the two receptors share the same signaling cascade, such as thyrotropin-releasing hormone (TRH) and angiotensin II (ANG II), are still far from being understood. Here, we analyzed hormone-induced Ca 2þ responses and the process of desensitization in HEK-293 cells, which express endogenous ANG II receptors. These cells were transfected to express exogenously high levels of TRH receptors (clone E2) or both TRH receptors and G 11 a protein (clone E2M11). We observed that the characteristics of the Ca 2þ response, as well as the process of desensitization, were both strongly dependent on receptor number and G 11 a protein level. Whereas treatment of E2 cells with TRH or ANG II led to significant desensitization of the Ca 2þ response to subsequent addition of either hormone, the response was not desensitized in E2M11 cells expressing high levels of G 11 a. In addition, stimulation of both cell lines with THR elicited a clear heterologous desensitization to subsequent stimulation with ANG II. On the other hand, ANG II did not affect a subsequent response to TRH. ANG II-mediated signal transduction was strongly dependent on plasma membrane integrity modified by cholesterol depletion, but signaling through TRH receptors was altered only slightly under these conditions. It may be concluded that the level of expression of G-protein-coupled receptors and their cognate G-proteins strongly influences not only the magnitude of the Ca 2þ response but also the process of desensitization and resistance to subsequent hormone addition.

Research paper thumbnail of Structure, function, and pharmacology of NMDA receptor channels

Physiological research / Academia Scientiarum Bohemoslovaca, 2014

NMDA receptors have received much attention over the last few decades, due to their role in many ... more NMDA receptors have received much attention over the last few decades, due to their role in many types of neural plasticity on the one hand, and their involvement in excitotoxicity on the other hand. There is great interest in developing clinically relevant NMDA receptor antagonists that would block excitotoxic NMDA receptor activation, without interfering with NMDA receptor function needed for normal synaptic transmission and plasticity. This review summarizes current understanding of the structure of NMDA receptors and the mechanisms of NMDA receptor activation and modulation, with special attention given to data describing the properties of various types of NMDA receptor inhibition. Our recent analyses point to certain neurosteroids as NMDA receptor inhibitors with desirable properties. Specifically, these compounds show use-dependent but voltage-independent block, that is predicted to preferentially target excessive tonic NMDA receptor activation. Importantly, neurosteroids are ...

Research paper thumbnail of Potassium buffering by Müller cells isolated from the center and periphery of the frog retina

Glia, 1999

Mü ller (radial glial) cells span the retina from the outer to the inner limiting membranes. They... more Mü ller (radial glial) cells span the retina from the outer to the inner limiting membranes. They are the only glial cells found in the amphibian retina. The thickness of the frog (Rana pipiens) retina decreases by a factor of about four from the center to the periphery. Thus, Mü ller cells were isolated, by enzymatic dissociation, with stalk lengths from 20 to 140 µm. Their ability to transfer K ϩ via the stalk between soma and endfoot was studied. Membrane currents were recorded using the whole-cell voltage-clamp technique with the pipette sealed to either the endfoot or the soma. Inward (I KIN ) or outward (I KO ) currents were elicited by rapid increases (3 to 10 mM) or decreases (3 to 1 mM) of the extracellular K ϩ concentration ([K ϩ ] o ) either by local application (close or distant to the recording pipette) or around the entire cell (whole cell perfusion). For the long central cells, the ratio I KIN /I KO was 4.6 Ϯ 0.6 SE (n ϭ 9) at the endfoot and 1.7 Ϯ 0.1 SE (n ϭ 8) at the soma. In cells from the retinal periphery, the ratio I KIN /I KO was higher, 7.0 Ϯ 0.27 (n ϭ 8) at the endfoot and 3.2 Ϯ 0.1 (n ϭ 10) at the soma. The results suggest that there is less inward rectification in the somatic than in the endfoot membrane. As expected from previous studies, the sensitivity of the cells to K ϩ was higher at the endfoot than at the soma. The amplitude of I KIN at the endfoot compared to the soma was about 8-fold for the long central cells but only about 1.5-fold for the short peripheral cells. Currents spread readily from endfoot to soma in the peripheral cells. In the long central Mü ller cells the soma and endfoot appeared electrotonically isolated. The ''functional length constant'', , of cell stalk processes was about 70 µm. The relative decrement of large inward currents was stronger than that of smaller outward currents; this difference (''artificial rectification'') is explained by a simple model, where larger currents (inward) are attenuated more than smaller (outward) currents. The data support the hypothesis that in the retinal periphery, Mü ller cells provide extensive spatial K ϩ buffering from both plexiform layers into the vitreous body. In the central retina, however, such currents are limited within a short (interlaminar) range.

Research paper thumbnail of Spatial distribution of spermine/spermidine content and K+-current rectification in frog retinal glial (M�ller) cells

Glia, 2000

Previous studies in retinal glial (Mü ller) cells have suggested that (1) the dominant membrane c... more Previous studies in retinal glial (Mü ller) cells have suggested that (1) the dominant membrane currents are mediated by K ϩ inward-rectifier (Kir) channels (Newman and Reichenbach, Trends Neurosci 19:307-312, 1996), and (2) rectification of these Kir channels is due largely to a block of outward currents by endogenous polyamines such as spermine/spermidine (SPM/SPD) (Lopatin et al., Nature 372:366 -369, 1994). In frog Mü ller cells, the degree of rectification of Kir-mediated currents is significantly higher in the endfoot than in the somatic membrane (Skatchkov et al., Glia 27:171-181, 1999). This article shows that in these cells there is a topographical correlation between the local cytoplasmic SPM/SPD immunoreactivity and the ratio of inward to outward K ϩ currents through the surrounding membrane area. Throughout the retina, Mü ller cell endfeet display a high SPM/SPD immunolabel (assessed by densitometry) and a large inward rectification of K ϩ currents, as measured by the ratio of inward to outward current produced by step changes in [K ϩ ] o . In the retinal periphery, Mü ller cell somata are characterized by roughly one-half of the SPM/SPD immunoreactivity and K ϩ -current rectification as the corresponding endfeet. In the retinal center, Mü ller cell somata are virtually devoid of both SPM/SPD immunolabel and K ϩ -current inward rectification. Comparing one region of the retina with another, we find an exponential correlation between the local K ϩ rectification and the local SPM/SPD content. This finding suggests that the degree of inward rectification in a given membrane area is determined by the local cytoplasmic polyamine concentration. GLIA 31: 84 -90, 2000.

Research paper thumbnail of Potassium buffering by Müller cells isolated from the center and periphery of the frog retina

Glia, 1999

Müller (radial glial) cells span the retina from the outer to the inner limiting membranes. They ... more Müller (radial glial) cells span the retina from the outer to the inner limiting membranes. They are the only glial cells found in the amphibian retina. The thickness of the frog (Rana pipiens) retina decreases by a factor of about four from the center to the periphery. Thus, Müller cells were isolated, by enzymatic dissociation, with stalk lengths from 20 to 140 microm. Their ability to transfer K(+) via the stalk between soma and endfoot was studied. Membrane currents were recorded using the whole-cell voltage-clamp technique with the pipette sealed to either the endfoot or the soma. Inward (I(KIN)) or outward (I(KO)) currents were elicited by rapid increases (3 to 10 mM) or decreases (3 to 1 mM) of the extracellular K(+) concentration ([K(+)](o)) either by local application (close or distant to the recording pipette) or around the entire cell (whole cell perfusion). For the long central cells, the ratio I(KIN)/I(KO) was 4.6 +/- 0.6 SE (n = 9) at the endfoot and 1.7 +/- 0.1 SE (n = 8) at the soma. In cells from the retinal periphery, the ratio I(KIN)/I(KO) was higher, 7.0 +/- 0.27 (n = 8) at the endfoot and 3.2 +/- 0.1 (n = 10) at the soma. The results suggest that there is less inward rectification in the somatic than in the endfoot membrane. As expected from previous studies, the sensitivity of the cells to K(+) was higher at the endfoot than at the soma. The amplitude of I(KIN) at the endfoot compared to the soma was about 8-fold for the long central cells but only about 1.5-fold for the short peripheral cells. Currents spread readily from endfoot to soma in the peripheral cells. In the long central Müller cells the soma and endfoot appeared electrotonically isolated. The "functional length constant", lambda, of cell stalk processes was about 70 microm. The relative decrement of large inward currents was stronger than that of smaller outward currents; this difference ("artificial rectification") is explained by a simple model, where larger currents (inward) are attenuated more than smaller (outward) currents. The data support the hypothesis that in the retinal periphery, Müller cells provide extensive spatial K(+) buffering from both plexiform layers into the vitreous body. In the central retina, however, such currents are limited within a short (interlaminar) range.

Research paper thumbnail of Spatial distribution of spermine/spermidine content and K+-current rectification in frog retinal glial (M�ller) cells

Glia, 2000

Previous studies in retinal glial (Mü ller) cells have suggested that (1) the dominant membrane c... more Previous studies in retinal glial (Mü ller) cells have suggested that (1) the dominant membrane currents are mediated by K ϩ inward-rectifier (Kir) channels (Newman and Reichenbach, Trends Neurosci 19:307-312, 1996), and (2) rectification of these Kir channels is due largely to a block of outward currents by endogenous polyamines such as spermine/spermidine (SPM/SPD) (Lopatin et al., Nature 372:366-369, 1994). In frog Mü ller cells, the degree of rectification of Kir-mediated currents is significantly higher in the endfoot than in the somatic membrane (Skatchkov et al., Glia 27:171-181, 1999). This article shows that in these cells there is a topographical correlation between the local cytoplasmic SPM/SPD immunoreactivity and the ratio of inward to outward K ϩ currents through the surrounding membrane area. Throughout the retina, Mü ller cell endfeet display a high SPM/SPD immunolabel (assessed by densitometry) and a large inward rectification of K ϩ currents, as measured by the ratio of inward to outward current produced by step changes in [K ϩ ] o. In the retinal periphery, Mü ller cell somata are characterized by roughly one-half of the SPM/SPD immunoreactivity and K ϩ-current rectification as the corresponding endfeet. In the retinal center, Mü ller cell somata are virtually devoid of both SPM/SPD immunolabel and K ϩ-current inward rectification. Comparing one region of the retina with another, we find an exponential correlation between the local K ϩ rectification and the local SPM/SPD content. This finding suggests that the degree of inward rectification in a given membrane area is determined by the local cytoplasmic polyamine concentration. GLIA 31:84-90, 2000.

Research paper thumbnail of The pharmacology of tacrine at N-methyl-d-aspartate receptors

Progress in neuro-psychopharmacology & biological psychiatry, Apr 3, 2017

The mechanism of tacrine as a precognitive drug has been considered to be complex and not fully u... more The mechanism of tacrine as a precognitive drug has been considered to be complex and not fully understood. It has been reported to involve a wide spectrum of targets involving cholinergic, gabaergic, nitrinergic and glutamatergic pathways. Here, we review the effect of tacrine and its derivatives on the NMDA receptors (NMDAR) with a focus on the mechanism of action and biological consequences related to the Alzheimer's disease treatment. Our findings indicate that effect of tacrine on glutamatergic neurons is both direct and indirect. Direct NMDAR antagonistic effect is often reported by in vitro studies; however, it is achieved by high tacrine concentrations which are not likely to occur under clinical conditions. The impact on memory and behavioral testing can be ascribed to indirect effects of tacrine caused by influencing the NMDAR-mediated currents via M1 receptor activation, which leads to inhibition of Ca(2+)-activated potassium channels. Such inhibition prevents membran...

Research paper thumbnail of Overexpression of the G protein G11α prevents desensitization of CA2+ response to thyrotropin-releasing hormone

Life Sciences, 1999

Doubly transfected human embryonal kidney cells (clone E2M11 of the HEK 293 cell line) expressing... more Doubly transfected human embryonal kidney cells (clone E2M11 of the HEK 293 cell line) expressing both thyrotropin-releasing hormone (TRH) receptors and Gll a protein in high amounts were used to analyze the desensitization phenomenon of the Ca"-mobiiig pathway. Quite unexpectedly, we did not observe any significant desensitization of the [Ca2']i response to TRH in these cells after repeated or prolonged incubation with the hormone (up to 5 h). Under the same conditions, the TRH-induced [Ca"]i response was completely desensitized in the parent cell line (293-E2 eels) expressing TRH receptors alone. In both cell lines, inositol phosphate response was desensitized after TRH exposure, although basal levels of inositol phospates in TRH-pretreated cells were much higher than in "naive" TRH-unexposed cells. These data suggest a significant role of the G protein GIla in desensitization of the Ca2'-mobilizing pathway occuring after repeated or long-term exposure of target cells to TRH-receptor agonists.

Research paper thumbnail of Ca2+ responses to thyrotropin-releasing hormone and angiotensin II: the role of plasma membrane integrity and effect of G11α protein overexpression on homologous and heterologous desensitization

Cell Biochemistry and Function, 2008

The molecular mechanisms involved in GPCR-initiated signaling cascades where the two receptors sh... more The molecular mechanisms involved in GPCR-initiated signaling cascades where the two receptors share the same signaling cascade, such as thyrotropin-releasing hormone (TRH) and angiotensin II (ANG II), are still far from being understood. Here, we analyzed hormone-induced Ca 2þ responses and the process of desensitization in HEK-293 cells, which express endogenous ANG II receptors. These cells were transfected to express exogenously high levels of TRH receptors (clone E2) or both TRH receptors and G 11 a protein (clone E2M11). We observed that the characteristics of the Ca 2þ response, as well as the process of desensitization, were both strongly dependent on receptor number and G 11 a protein level. Whereas treatment of E2 cells with TRH or ANG II led to significant desensitization of the Ca 2þ response to subsequent addition of either hormone, the response was not desensitized in E2M11 cells expressing high levels of G 11 a. In addition, stimulation of both cell lines with THR elicited a clear heterologous desensitization to subsequent stimulation with ANG II. On the other hand, ANG II did not affect a subsequent response to TRH. ANG II-mediated signal transduction was strongly dependent on plasma membrane integrity modified by cholesterol depletion, but signaling through TRH receptors was altered only slightly under these conditions. It may be concluded that the level of expression of G-protein-coupled receptors and their cognate G-proteins strongly influences not only the magnitude of the Ca 2þ response but also the process of desensitization and resistance to subsequent hormone addition.

Research paper thumbnail of Structure, function, and pharmacology of NMDA receptor channels

Physiological research / Academia Scientiarum Bohemoslovaca, 2014

NMDA receptors have received much attention over the last few decades, due to their role in many ... more NMDA receptors have received much attention over the last few decades, due to their role in many types of neural plasticity on the one hand, and their involvement in excitotoxicity on the other hand. There is great interest in developing clinically relevant NMDA receptor antagonists that would block excitotoxic NMDA receptor activation, without interfering with NMDA receptor function needed for normal synaptic transmission and plasticity. This review summarizes current understanding of the structure of NMDA receptors and the mechanisms of NMDA receptor activation and modulation, with special attention given to data describing the properties of various types of NMDA receptor inhibition. Our recent analyses point to certain neurosteroids as NMDA receptor inhibitors with desirable properties. Specifically, these compounds show use-dependent but voltage-independent block, that is predicted to preferentially target excessive tonic NMDA receptor activation. Importantly, neurosteroids are ...

Research paper thumbnail of Potassium buffering by Müller cells isolated from the center and periphery of the frog retina

Glia, 1999

Mü ller (radial glial) cells span the retina from the outer to the inner limiting membranes. They... more Mü ller (radial glial) cells span the retina from the outer to the inner limiting membranes. They are the only glial cells found in the amphibian retina. The thickness of the frog (Rana pipiens) retina decreases by a factor of about four from the center to the periphery. Thus, Mü ller cells were isolated, by enzymatic dissociation, with stalk lengths from 20 to 140 µm. Their ability to transfer K ϩ via the stalk between soma and endfoot was studied. Membrane currents were recorded using the whole-cell voltage-clamp technique with the pipette sealed to either the endfoot or the soma. Inward (I KIN ) or outward (I KO ) currents were elicited by rapid increases (3 to 10 mM) or decreases (3 to 1 mM) of the extracellular K ϩ concentration ([K ϩ ] o ) either by local application (close or distant to the recording pipette) or around the entire cell (whole cell perfusion). For the long central cells, the ratio I KIN /I KO was 4.6 Ϯ 0.6 SE (n ϭ 9) at the endfoot and 1.7 Ϯ 0.1 SE (n ϭ 8) at the soma. In cells from the retinal periphery, the ratio I KIN /I KO was higher, 7.0 Ϯ 0.27 (n ϭ 8) at the endfoot and 3.2 Ϯ 0.1 (n ϭ 10) at the soma. The results suggest that there is less inward rectification in the somatic than in the endfoot membrane. As expected from previous studies, the sensitivity of the cells to K ϩ was higher at the endfoot than at the soma. The amplitude of I KIN at the endfoot compared to the soma was about 8-fold for the long central cells but only about 1.5-fold for the short peripheral cells. Currents spread readily from endfoot to soma in the peripheral cells. In the long central Mü ller cells the soma and endfoot appeared electrotonically isolated. The ''functional length constant'', , of cell stalk processes was about 70 µm. The relative decrement of large inward currents was stronger than that of smaller outward currents; this difference (''artificial rectification'') is explained by a simple model, where larger currents (inward) are attenuated more than smaller (outward) currents. The data support the hypothesis that in the retinal periphery, Mü ller cells provide extensive spatial K ϩ buffering from both plexiform layers into the vitreous body. In the central retina, however, such currents are limited within a short (interlaminar) range.

Research paper thumbnail of Spatial distribution of spermine/spermidine content and K+-current rectification in frog retinal glial (M�ller) cells

Glia, 2000

Previous studies in retinal glial (Mü ller) cells have suggested that (1) the dominant membrane c... more Previous studies in retinal glial (Mü ller) cells have suggested that (1) the dominant membrane currents are mediated by K ϩ inward-rectifier (Kir) channels (Newman and Reichenbach, Trends Neurosci 19:307-312, 1996), and (2) rectification of these Kir channels is due largely to a block of outward currents by endogenous polyamines such as spermine/spermidine (SPM/SPD) (Lopatin et al., Nature 372:366 -369, 1994). In frog Mü ller cells, the degree of rectification of Kir-mediated currents is significantly higher in the endfoot than in the somatic membrane (Skatchkov et al., Glia 27:171-181, 1999). This article shows that in these cells there is a topographical correlation between the local cytoplasmic SPM/SPD immunoreactivity and the ratio of inward to outward K ϩ currents through the surrounding membrane area. Throughout the retina, Mü ller cell endfeet display a high SPM/SPD immunolabel (assessed by densitometry) and a large inward rectification of K ϩ currents, as measured by the ratio of inward to outward current produced by step changes in [K ϩ ] o . In the retinal periphery, Mü ller cell somata are characterized by roughly one-half of the SPM/SPD immunoreactivity and K ϩ -current rectification as the corresponding endfeet. In the retinal center, Mü ller cell somata are virtually devoid of both SPM/SPD immunolabel and K ϩ -current inward rectification. Comparing one region of the retina with another, we find an exponential correlation between the local K ϩ rectification and the local SPM/SPD content. This finding suggests that the degree of inward rectification in a given membrane area is determined by the local cytoplasmic polyamine concentration. GLIA 31: 84 -90, 2000.