Gerard Heck - Academia.edu (original) (raw)
Papers by Gerard Heck
Chemical Senses, Feb 21, 2011
Journal of Neurophysiology, Oct 1, 1993
1. Chorda tympani (CT) neural responses to NaCl were recorded while the potential across the apic... more 1. Chorda tympani (CT) neural responses to NaCl were recorded while the potential across the apical membrane of taste cells was perturbed by voltage clamp in rats fed a Na(+)-restricted diet pre- and postnatally (Na(+)-restricted rats) and in controls. 2. Control rats gave CT responses that were enhanced at negative voltage clamp and suppressed at positive voltage clamp. In contrast, CT responses from Na(+)-restricted rats were virtually voltage insensitive. 3. Analysis of the voltage-sensitivity of the CT response shows that Na(+)-restricted rats have < 10% of the density of functional apical Na+ channels normally present in control rats demonstrating that early dietary Na(+)-restriction prevents the functional expression of these key elements in salt taste transduction. Furthermore, the data demonstrate the value of this technique in assessing involvement of distinct cellular domains in taste transduction.
Chemical Senses, 1980
Abstract We have compared the surface active properties of gymnemic acid with those of the wellkn... more Abstract We have compared the surface active properties of gymnemic acid with those of the wellknown surfactant sodium lauryl sulfate. Aqueous solutions of gymnemic acid produce a surface tension-concentration relation similar to that of water soluble surfactants. Its form ...
The Journal of General Physiology, May 1, 1984
Chemical Senses, 1984
ABSTRACT
Journal of Neurophysiology, Mar 1, 1997
Journal of Neurophysiology, Sep 1, 2007
The Journal of Physiology, Mar 30, 2004
The role of basolateral Na+–H+ exchanger isoform-1 (NHE-1) was investigated in neural adaptation ... more The role of basolateral Na+–H+ exchanger isoform-1 (NHE-1) was investigated in neural adaptation of rat taste responses to acidic stimuli, by direct measurement of intracellular pH (pHi) in polarized taste receptor cells (TRCs) and by chorda tympani (CT) taste nerve recordings. In TRCs perfused with CO2/HCO3−-free solution (pH 7.4), removal of basolateral Na+ decreased pHi reversibly and zoniporide, a specific NHE-1 blocker, inhibited the Na+-induced changes in pHi. The spontaneous rate of TRC pHi recovery from NH4Cl pulses was inhibited by basolateral zoniporide with a Ki of 0.33μm. Exposure to basolateral ionomycin, reversibly increased TRC Ca2+, resting pHi, and the spontaneous rate of pHi recovery from an NH4Cl pulse. These effects of Ca2+ on pHi were blocked by zoniporide. In in vivo experiments, topical lingual application of zoniporide increased the magnitude of the CT responses to acetic acid and CO2, but not to HCl. Topical lingual application of ionomycin did not affect the phasic part of the CT responses to acidic stimuli, but decreased the tonic part by 50% of control over a period of about 1 min. This increased adaptation in the CT response was inhibited by zoniporide. Topical lingual application of 8-CPT-cAMP increased the CT responses to HCl, but not to CO2, and acetic acid. In the presence of cAMP, ionomycin increased sensory adaptation to HCl, CO2, and acetic acid. Thus, cAMP and Ca2+ independently modulate CT responses to acidic stimuli. While cAMP enhances TRC apical H+ entry and CT responses to strong acid, an increase in Ca2+ activates NHE-1, and increases neural adaptation to all acidic stimuli.
The Journal of General Physiology, Jul 1, 1988
The Journal of General Physiology, Nov 1, 1994
Science, Nov 1, 1991
Sodium salts are potent taste stimuli, but their effectiveness is markedly dependent on the anion... more Sodium salts are potent taste stimuli, but their effectiveness is markedly dependent on the anion, with chloride yielding the greatest response. The cellular mechanisms that mediate this phenomenon are not known. This "anion paradox" has been resolved by considering the field potential that is generated by restricted electrodiffusion of the anion through paracellular shunts between taste-bud cells. Neural responses to sodium chloride, sodium acetate, and sodium gluconate were studied while the field potential was voltage-clamped. Clamping at electronegative values eliminated the anion effect, whereas clamping at electropositive potentials exaggerated it. Thus, field potentials across the lingual epithelium modulate taste reception, indicating that the functional unit of taste reception includes the taste cell and its paracellular microenvironment.
Journal of Neurophysiology, May 1, 1996
1. Chorda tympani (CT) nerve responses were recorded during simultaneous current and voltage clam... more 1. Chorda tympani (CT) nerve responses were recorded during simultaneous current and voltage clamping of the lingual receptive-field epithelium to examine the role of field potential in taste mixture suppression between sodium gluconate (NaG) and potassium gluconate (KG). 2. Under zero current-clamp conditions, CT responses to 100 mM NaG were suppressed by 63% when presented in mixture with 250 mM KG. At this concentration, KG alone elicited no measurable neural activity, but produced a large submucosal-positive field potential. 3. When CT responses to 100 mM NaG were obtained with voltage clamp at the zero-current clamp field potential of the NaG/KG mixture, they were suppressed by only 30% relative to NaG responses under zero-current clamp. Similarly, CT responses to the mixture of NaG and KG measured while voltage was clamped at the field potential of NaG alone were slightly elevated, but not to the magnitude of zero-current clamp responses to NaG. Therefore field potential-mediated suppression of CT responses to NaG accounts for only a part of the total mixture suppression between NaG and KG. 4. Analysis of the voltage dependence of CT responses to NaG indicated that the moderate field potential increase (8.9 mV) caused by the presence of KG in the mixture equates to a 43% increase in the apparent Km for NaG, from 110 to 157 mM. Use of this effective Km obviated the effect of field potential on CT responses to the NaG/KG mixture and permitted kinetic analysis of K+ blockade of Na+ responses. These analyses suggested that K ions block Na+ movement through apical Na+ channels in a voltage-independent manner with an apparent Ko of 405 mM. Importantly, direct inhibition of Na+ transduction by K+ can account for the part of mixture suppression not mediated by field potential. 5. These experiments reveal that mixture suppression between NaG and KG is derived from two distinct sources. Field potential, triggered largely by the limited mobility of both K+ and Na+ through taste bud tight junctions, globally modulates Na+ transduction. In addition, at the level of the apical Na+ channel, K ions directly block movement of depolarizing Na+ across taste receptor apical membranes.
Journal of Neurophysiology, Feb 1, 1998
Biophysical Journal, Mar 1, 1980
Advances in chemistry series, Jun 1, 1980
Chemical Senses, 1980
Abstract. We present an analysis of stimulus transport in mammalian taste reception emphasizing t... more Abstract. We present an analysis of stimulus transport in mammalian taste reception emphasizing the coupling between hydrodynamic and diffusive mass transfer. We show that flow-rate dependence in the phasic portions of the gustatory response can be explained by a flow-velocity dependent diffusion-boundary layer in series with a flow-indifferent path length. Using data from the literature we show that the concentration dependence of the neural latency to NaCl stimulation in the rat and the threshold concentration can be accounted for by the time course of stimulus arrival and need not imp-ly a uniquely slow sensory transduction process. We develop a generalized response function which describes aspects of the early phasic neural response and shows that early events are governed solely by the local concentration of stimulus. This too is confirmed by data in the literature. The surface pressure is characterized as an example of a nonmonotonic response function which can account for the general properties of the salt, acid and water response. In vitro studies on phopholipid monolayers conform to the theory. It is suggested that surface activity may be critical in transduction and that sur-face active agents can have profound effects on taste reception.
Journal of Neurophysiology, Jul 1, 1993
1. Voltage-clamp and current-clamp data were obtained from a circumscribed region of the anterior... more 1. Voltage-clamp and current-clamp data were obtained from a circumscribed region of the anterior rat lingual epithelium while simultaneously monitoring the afferent, stimulus-evoked, neural response from the same receptive field. 2. Chorda tympani (CT) responses at constant Na(+)-salt concentration were enhanced by submucosa negative voltage clamp and suppressed by positive voltage clamp. The complete CT response profile, including the time course of adaptation, was not uniquely determined by NaCl concentration alone. The response could be reproduced at different NaCl concentrations by applying a compensating voltage. 3. The form of the concentration and voltage dependence of the CT response indicates that the complete stimulus energy is the Na+ electrochemical potential difference across receptor cell apical membranes, and not Na+ concentration alone. This is the underlying principal behind the equivalence of chemical and electric taste for Na+ salts. 4. CT responses to sodium gluconate (25 and 200 mM) and 25 mM NaCl produced amiloride-insensitive components (AIC) of low magnitude. NaCl at 200 mM produced a significantly larger AIC. The AIC was voltage-clamp independent. The relative magnitude of the AIC was positively correlated with the transepithelial conductance of each salt. This suggests that the large AIC for 200 mM NaCl results from its relatively high permeability through the paracellular pathway. 5. Analysis of the CT response under voltage clamp revealed two anion effects on Na(+)-salt taste, both of which act through the paracellular shunt. 1) Anions modify the transepithelial potential (TP) across tight junctions and thereby modulate the cell receptor potential. This anion effect can be eliminated by voltage clamping the TP. 2) Sufficiently mobile anions facilitate electroneutral diffusion of Na+ salts through tight junctions. This effect is observed especially when Cl- is the anion and when the stimulus concentration favors NaCl influx, allowing Na+ to stimulate receptor cells from the submucosal side. Because the submucosal intercellular spaces are nearly isopotential regions, this effect is insensitive to voltage clamp of the TP. The large AIC associated with this anion effect is due to the low permeability of amiloride.
Chemical Senses, May 7, 2015
Experimental data indicate that the Na ion taste receptor is a Na selective membrane ion channel.... more Experimental data indicate that the Na ion taste receptor is a Na selective membrane ion channel. This channel appears to have passive properties (it is not voltage-gated). Sodium ions stimulate receptor cells by entering them directly down a favorable electrochemical potential gradient and thereby depolarizing the cells. This presumably leads to the release of neurotransmitter, thereby causing excitation of the taste nerves. This process may require the intervention of voltage-gated Na channels that may depolarize the cells sufficiently to activate Ca channels necessary for Ca entry into the cells prior to the release of neurotransmitter. Anions may either augment or impede the movement of Na, depending on their paracellular permeabilities. The electrical potential across the taste buds, controlled in part by anion permeability across the tight junctions, may be one of the regulatory factors in the release of neurotransmitter.<<ETX>>
Chemical Senses, Feb 21, 2011
Journal of Neurophysiology, Oct 1, 1993
1. Chorda tympani (CT) neural responses to NaCl were recorded while the potential across the apic... more 1. Chorda tympani (CT) neural responses to NaCl were recorded while the potential across the apical membrane of taste cells was perturbed by voltage clamp in rats fed a Na(+)-restricted diet pre- and postnatally (Na(+)-restricted rats) and in controls. 2. Control rats gave CT responses that were enhanced at negative voltage clamp and suppressed at positive voltage clamp. In contrast, CT responses from Na(+)-restricted rats were virtually voltage insensitive. 3. Analysis of the voltage-sensitivity of the CT response shows that Na(+)-restricted rats have < 10% of the density of functional apical Na+ channels normally present in control rats demonstrating that early dietary Na(+)-restriction prevents the functional expression of these key elements in salt taste transduction. Furthermore, the data demonstrate the value of this technique in assessing involvement of distinct cellular domains in taste transduction.
Chemical Senses, 1980
Abstract We have compared the surface active properties of gymnemic acid with those of the wellkn... more Abstract We have compared the surface active properties of gymnemic acid with those of the wellknown surfactant sodium lauryl sulfate. Aqueous solutions of gymnemic acid produce a surface tension-concentration relation similar to that of water soluble surfactants. Its form ...
The Journal of General Physiology, May 1, 1984
Chemical Senses, 1984
ABSTRACT
Journal of Neurophysiology, Mar 1, 1997
Journal of Neurophysiology, Sep 1, 2007
The Journal of Physiology, Mar 30, 2004
The role of basolateral Na+–H+ exchanger isoform-1 (NHE-1) was investigated in neural adaptation ... more The role of basolateral Na+–H+ exchanger isoform-1 (NHE-1) was investigated in neural adaptation of rat taste responses to acidic stimuli, by direct measurement of intracellular pH (pHi) in polarized taste receptor cells (TRCs) and by chorda tympani (CT) taste nerve recordings. In TRCs perfused with CO2/HCO3−-free solution (pH 7.4), removal of basolateral Na+ decreased pHi reversibly and zoniporide, a specific NHE-1 blocker, inhibited the Na+-induced changes in pHi. The spontaneous rate of TRC pHi recovery from NH4Cl pulses was inhibited by basolateral zoniporide with a Ki of 0.33μm. Exposure to basolateral ionomycin, reversibly increased TRC Ca2+, resting pHi, and the spontaneous rate of pHi recovery from an NH4Cl pulse. These effects of Ca2+ on pHi were blocked by zoniporide. In in vivo experiments, topical lingual application of zoniporide increased the magnitude of the CT responses to acetic acid and CO2, but not to HCl. Topical lingual application of ionomycin did not affect the phasic part of the CT responses to acidic stimuli, but decreased the tonic part by 50% of control over a period of about 1 min. This increased adaptation in the CT response was inhibited by zoniporide. Topical lingual application of 8-CPT-cAMP increased the CT responses to HCl, but not to CO2, and acetic acid. In the presence of cAMP, ionomycin increased sensory adaptation to HCl, CO2, and acetic acid. Thus, cAMP and Ca2+ independently modulate CT responses to acidic stimuli. While cAMP enhances TRC apical H+ entry and CT responses to strong acid, an increase in Ca2+ activates NHE-1, and increases neural adaptation to all acidic stimuli.
The Journal of General Physiology, Jul 1, 1988
The Journal of General Physiology, Nov 1, 1994
Science, Nov 1, 1991
Sodium salts are potent taste stimuli, but their effectiveness is markedly dependent on the anion... more Sodium salts are potent taste stimuli, but their effectiveness is markedly dependent on the anion, with chloride yielding the greatest response. The cellular mechanisms that mediate this phenomenon are not known. This "anion paradox" has been resolved by considering the field potential that is generated by restricted electrodiffusion of the anion through paracellular shunts between taste-bud cells. Neural responses to sodium chloride, sodium acetate, and sodium gluconate were studied while the field potential was voltage-clamped. Clamping at electronegative values eliminated the anion effect, whereas clamping at electropositive potentials exaggerated it. Thus, field potentials across the lingual epithelium modulate taste reception, indicating that the functional unit of taste reception includes the taste cell and its paracellular microenvironment.
Journal of Neurophysiology, May 1, 1996
1. Chorda tympani (CT) nerve responses were recorded during simultaneous current and voltage clam... more 1. Chorda tympani (CT) nerve responses were recorded during simultaneous current and voltage clamping of the lingual receptive-field epithelium to examine the role of field potential in taste mixture suppression between sodium gluconate (NaG) and potassium gluconate (KG). 2. Under zero current-clamp conditions, CT responses to 100 mM NaG were suppressed by 63% when presented in mixture with 250 mM KG. At this concentration, KG alone elicited no measurable neural activity, but produced a large submucosal-positive field potential. 3. When CT responses to 100 mM NaG were obtained with voltage clamp at the zero-current clamp field potential of the NaG/KG mixture, they were suppressed by only 30% relative to NaG responses under zero-current clamp. Similarly, CT responses to the mixture of NaG and KG measured while voltage was clamped at the field potential of NaG alone were slightly elevated, but not to the magnitude of zero-current clamp responses to NaG. Therefore field potential-mediated suppression of CT responses to NaG accounts for only a part of the total mixture suppression between NaG and KG. 4. Analysis of the voltage dependence of CT responses to NaG indicated that the moderate field potential increase (8.9 mV) caused by the presence of KG in the mixture equates to a 43% increase in the apparent Km for NaG, from 110 to 157 mM. Use of this effective Km obviated the effect of field potential on CT responses to the NaG/KG mixture and permitted kinetic analysis of K+ blockade of Na+ responses. These analyses suggested that K ions block Na+ movement through apical Na+ channels in a voltage-independent manner with an apparent Ko of 405 mM. Importantly, direct inhibition of Na+ transduction by K+ can account for the part of mixture suppression not mediated by field potential. 5. These experiments reveal that mixture suppression between NaG and KG is derived from two distinct sources. Field potential, triggered largely by the limited mobility of both K+ and Na+ through taste bud tight junctions, globally modulates Na+ transduction. In addition, at the level of the apical Na+ channel, K ions directly block movement of depolarizing Na+ across taste receptor apical membranes.
Journal of Neurophysiology, Feb 1, 1998
Biophysical Journal, Mar 1, 1980
Advances in chemistry series, Jun 1, 1980
Chemical Senses, 1980
Abstract. We present an analysis of stimulus transport in mammalian taste reception emphasizing t... more Abstract. We present an analysis of stimulus transport in mammalian taste reception emphasizing the coupling between hydrodynamic and diffusive mass transfer. We show that flow-rate dependence in the phasic portions of the gustatory response can be explained by a flow-velocity dependent diffusion-boundary layer in series with a flow-indifferent path length. Using data from the literature we show that the concentration dependence of the neural latency to NaCl stimulation in the rat and the threshold concentration can be accounted for by the time course of stimulus arrival and need not imp-ly a uniquely slow sensory transduction process. We develop a generalized response function which describes aspects of the early phasic neural response and shows that early events are governed solely by the local concentration of stimulus. This too is confirmed by data in the literature. The surface pressure is characterized as an example of a nonmonotonic response function which can account for the general properties of the salt, acid and water response. In vitro studies on phopholipid monolayers conform to the theory. It is suggested that surface activity may be critical in transduction and that sur-face active agents can have profound effects on taste reception.
Journal of Neurophysiology, Jul 1, 1993
1. Voltage-clamp and current-clamp data were obtained from a circumscribed region of the anterior... more 1. Voltage-clamp and current-clamp data were obtained from a circumscribed region of the anterior rat lingual epithelium while simultaneously monitoring the afferent, stimulus-evoked, neural response from the same receptive field. 2. Chorda tympani (CT) responses at constant Na(+)-salt concentration were enhanced by submucosa negative voltage clamp and suppressed by positive voltage clamp. The complete CT response profile, including the time course of adaptation, was not uniquely determined by NaCl concentration alone. The response could be reproduced at different NaCl concentrations by applying a compensating voltage. 3. The form of the concentration and voltage dependence of the CT response indicates that the complete stimulus energy is the Na+ electrochemical potential difference across receptor cell apical membranes, and not Na+ concentration alone. This is the underlying principal behind the equivalence of chemical and electric taste for Na+ salts. 4. CT responses to sodium gluconate (25 and 200 mM) and 25 mM NaCl produced amiloride-insensitive components (AIC) of low magnitude. NaCl at 200 mM produced a significantly larger AIC. The AIC was voltage-clamp independent. The relative magnitude of the AIC was positively correlated with the transepithelial conductance of each salt. This suggests that the large AIC for 200 mM NaCl results from its relatively high permeability through the paracellular pathway. 5. Analysis of the CT response under voltage clamp revealed two anion effects on Na(+)-salt taste, both of which act through the paracellular shunt. 1) Anions modify the transepithelial potential (TP) across tight junctions and thereby modulate the cell receptor potential. This anion effect can be eliminated by voltage clamping the TP. 2) Sufficiently mobile anions facilitate electroneutral diffusion of Na+ salts through tight junctions. This effect is observed especially when Cl- is the anion and when the stimulus concentration favors NaCl influx, allowing Na+ to stimulate receptor cells from the submucosal side. Because the submucosal intercellular spaces are nearly isopotential regions, this effect is insensitive to voltage clamp of the TP. The large AIC associated with this anion effect is due to the low permeability of amiloride.
Chemical Senses, May 7, 2015
Experimental data indicate that the Na ion taste receptor is a Na selective membrane ion channel.... more Experimental data indicate that the Na ion taste receptor is a Na selective membrane ion channel. This channel appears to have passive properties (it is not voltage-gated). Sodium ions stimulate receptor cells by entering them directly down a favorable electrochemical potential gradient and thereby depolarizing the cells. This presumably leads to the release of neurotransmitter, thereby causing excitation of the taste nerves. This process may require the intervention of voltage-gated Na channels that may depolarize the cells sufficiently to activate Ca channels necessary for Ca entry into the cells prior to the release of neurotransmitter. Anions may either augment or impede the movement of Na, depending on their paracellular permeabilities. The electrical potential across the taste buds, controlled in part by anion permeability across the tight junctions, may be one of the regulatory factors in the release of neurotransmitter.<<ETX>>