Robert Pinnock - Academia.edu (original) (raw)
Papers by Robert Pinnock
iv) ACKNOWLEDGEMENTS (v) ABBREVIATIONS ( CHAPTER ONE. INTRODUCTION 1. Substance P 1 1.1. Isolatio... more iv) ACKNOWLEDGEMENTS (v) ABBREVIATIONS ( CHAPTER ONE. INTRODUCTION 1. Substance P 1 1.1. Isolation and structure 1 1.2. Distribution of substance P in the brain 1 1.3. Structure activity studies in peripheral preparations 1 1.4. Structure activity relationships in the CNS 2 1.5. Metabolism of substance P 3 1.6. Mechanism of action 4 1.7. Possible role of substance P in the CNS 5 2. Melanocyte stimulating hormone release inhibitory factor (MIF) 8 2.1. General pharmacology of MIF 8 2.2. Interactions of MSH and MIF with dopamine 8 3 Thyrotropin releasing hormone (TRH) 12 3.1. General pharmacology of TRH 12 3.2. TRH in the CNS 12 k. Opioid peptides I6 4.1. Opioid peptides in the CNS 16 U.2. Interactions between dopamine and opiates I6 5. Dopamine 19 5.1. Dopamine, distribution and pathways in the CNS 19 5.2. Biochemistry of dopamine release, receptor binding and postsynaptic actions I9 5.3. lontophoretic dopamine pharmacology in the caudate nucleus and nucleus accumbens 20 5.4. Effect o...
Journal of Experimental Biology
N-Methyl lycaconitine is the most effective low molecular weight antagonist reported for an insec... more N-Methyl lycaconitine is the most effective low molecular weight antagonist reported for an insect neuronal nicotinic receptor. In the present study, the citrate salt of this neurotoxin from the plant Delphinium brownii was found to inhibit [3H]-α-bungarotoxin binding to nerve cord extracts of the cockroach Periplaneta americana with a Ki of l.4×10−9moll−1. At a concentration of 1.0×10−7moll−1, N-methyl lycaconitine completely blocked the response to ionophoretically applied acetylcholine recorded from the cell body membrane of the fast coxal depressor motor neurone (Df) in the desheathed metathoracic ganglion of the cockroach. The block was voltage-independent over the range of membrane potential −100 to −30 mV. The effectiveness of N-methyl lycaconitine on the nicotinic receptor, which is present in very high concentrations in the insect nervous system, suggests that this alkaloid is a natural plant protection agent.
Cell Calcium, Aug 1, 1998
In human U373 MG astrocytoma cells, histamine and substance P stimulated similar peak increases i... more In human U373 MG astrocytoma cells, histamine and substance P stimulated similar peak increases in intracellular free calcium concentrations ([Ca2+]i), as measured by single cell imaging of Fura-2 fluorescence. Best-fit EC50 values for the peak Ca2+ response were 1.86 microM for histamine and 0.93 nM for substance P. The histamine Ca2+ response was manifest as either a series of repetitive spikes, or, at higher concentrations, a peak followed by a lower plateau level of Ca2+. In contrast, the substance P response became more transient at higher agonist concentrations. Substance P (10 nM) stimulated a biphasic increase in levels of inositol (1,4,5) trisphosphate (Ins(1,4,5)P3) with a peak of 97 +/- 5 pmoles/mg protein at 10 s. In contrast, the Ins(1,4,5)P3 response to 100 microM histamine was only marginally above basal levels of around 12 pmoles/mg protein. However, concentrations of histamine and substance P giving similar Ins(1,4,5)P3 responses produce similar peak increases in [Ca2+]i. HPLC analysis indicated that histamine stimulated the production of [3H]-Ins(1,4,5)P3 and its metabolites, although the magnitude of response was smaller than that observed with substance P. The initial Ca2+ responses to histamine and substance P did not require the presence of extracellular Ca2+. The Ca2+ response to histamine was unaffected by treatment with ryanodine, and was shifted to areas of lower agonist concentration by thimerosal. These results demonstrate that extremely small increases in Ins(1,4,5)P3 can stimulate large increases in [Ca2+]i in U373 MG cells, and suggest a marked redundancy for Ins(1,4,5)P3 production in the Ca2+ signalling pathway.
Pflugers Arch Eur J Physiol, 2001
Hypertrophy is an adaptive response of the heart to myocardial injury or hemodynamic overload tha... more Hypertrophy is an adaptive response of the heart to myocardial injury or hemodynamic overload that may progress and contribute to cardiac decompensation and eventually to heart failure. The signaling pathways controlling this response in the cardiac myocyte are poorly understood. A data mining effort of a human failed heart cDNA library was undertaken in an effort to identify novel signaling molecules involved in cardiac hypertrophy. This effort identified a novel kinase (MLK7) homologous to the mixed lineage kinase family of proteins. The mixed lineage kinases are mitogenactivated protein kinase kinase kinases (MAPKKKs) which activate stress activated protein kinase/c-Jun Nterminal kinase (SAPK/JNK) and p38 kinase pathways. They contain a catalytic domain with homology to both serine/threonine and tyrosine-specific kinases and a dual leucine zipper. MLK7 is identical to leucine zipper and sterile-alpha motif protein kinase (ZAK) through the leucine zipper domain but has a completely divergent COOH-terminus and shares approximately 40% homology with the other MLKs overall. Expression of MLK7 mRNA is most abundant in skeletal muscle and heart, with expression restricted to the cardiac myocyte. The recombinant histidine tagged MLK7 expressed and purified from insect cells exhibited serine/ threonine kinase activity in vitro with myelin basic protein as substrate. When expressed in cardiac myocytes, MLK7 activated SAPK/JNK1, and ERK and p38 to a lesser extent. Additionally, MLK7 altered fetal gene expression and increased protein synthesis in cardiac myocytes. These data suggest that MLK7 is a new member of the mixed lineage kinase family that modulates cardiac SAPK/JNK pathway and may play a role in cardiac hypertrophy and progression to heart failure.
Neuropharmacology, 1983
Neurones in the substantia nigra were found to be sensitive to iontophoretically applied substanc... more Neurones in the substantia nigra were found to be sensitive to iontophoretically applied substance P, substance P 1-9 methyl ester and substance P 1-9 amide. Substance P 1-2, 4-9 and 5-9 methyl esters, thyrotropin releasing hormone (TRH), Pyroglutamyl-histidyl-2 methyl prolineamide (methyl TRH), Pyroglutamyl-histidyl-2 methyl prolineamide (methyl TRH), histidyl-proline-diketopiperazine (His-Pro) and MSH releasing inhibiting factor (MIF) were without effect on neurones in this area. Thyrotropin releasing hormone (TRH), methyl TRH, His-Pro and MIF were inactive on neurones in the caudate nucleus and nucleus accumbens. Bilateral injections of substance P and substance P 1-9 methyl ester into the ventral tegmental area (VTA) of conscious rats produced locomotor activity, while similar injections of substance P 4-9 and 5-9 methyl esters did not. The locomotor activity produced by amphetamine was prolonged by TRH, while MIF was devoid of such activity. The data suggest that substance P an...
The Journal of physiology, 1991
1. The effects on dorsal raphe neurones of the peptides bombesin, gastrin-releasing peptide and n... more 1. The effects on dorsal raphe neurones of the peptides bombesin, gastrin-releasing peptide and neuromedin B were studied using intracellular recording techniques from slices of rat brain maintained in vitro. The peptides were added to the solutions perfusing the slices. 2. The peptides bombesin, gastrin-releasing peptide and neuromedin B depolarized neurones in the dorsal raphe nucleus. The same neurones were depolarized by phenylephrine and hyperpolarized by 5-hydroxytryptamine (5-HT) but were insensitive to sulphated cholecystokinin octapeptide (CCK). 3. The responses to the peptides were not blocked by CCKA, CCKB and alpha 1-adrenoreceptor antagonists. 4. The response to the peptides persisted in the presence of tetrodotoxin (TTX) and low-calcium, high-magnesium-containing artificial cerebrospinal fluid (ACSF). 5. Under voltage clamp conditions the peptides caused a decrease in membrane conductance accompanied by an inward current. The reversal potential for the event was the sa...
Neuropharmacology, 2002
We have used the whole cell patch clamp method and fura-2 fluorescence imaging to study the actio... more We have used the whole cell patch clamp method and fura-2 fluorescence imaging to study the actions of gabapentin (1-(aminoethyl) cyclohexane acetic acid) on voltage-activated Ca(2+) entry into neonatal cultured dorsal root ganglion (DRG) neurones and differentiated F-11 (embryonic rat DRG x neuroblastoma hybrid) cells. Gabapentin (2.5 microM) in contrast to GABA (10 microM) did not influence resting membrane potential or input resistance. In current clamp mode gabapentin failed to influence the properties of evoked single action potentials but did reduce the duration of action potentials prolonged by Ba(2+). Gabapentin attenuated high voltage-activated Ca(2+) channel currents in a dose- and voltage- dependent manner in DRG neurones and reduced Ca(2+) influx evoked by K(+) depolarisation in differentiated F-11 cells loaded with fura-2. The sensitivity of DRG neurones to gabapentin was not changed by the GABA(B) receptor antagonist saclofen but pertussis toxin pre-treatment reduced t...
Molecular pharmacology, 1999
Although activation of G protein-coupled inward rectifying K+ (GIRK) channels by Gi/Go-coupled re... more Although activation of G protein-coupled inward rectifying K+ (GIRK) channels by Gi/Go-coupled receptors has been shown to be important in postsynaptic inhibition in the central nervous system, there is also evidence to suggest that inhibition of GIRK channels by Gq-coupled receptors is involved in postsynaptic excitation. In the present study we addressed whether the Gq-coupled receptors of the bombesin family can couple to GIRK channels and examined the mechanism by which this process occurs. Different combinations of GIRK channel subunits (Kir3.1, Kir3.2, and Kir3.4) and bombesin receptors (BB1 and BB2) were expressed in Xenopus oocytes. In all combinations tested GIRK currents were reversibly inhibited upon application of the bombesin-related peptides, neuromedin B or gastrin-releasing peptide in a concentration-dependent manner. Incubation of oocytes in the phospholipase C inhibitor U73122 or the protein kinase C (PKC) inhibitors chelerythrine and staurosporine significantly re...
![Research paper thumbnail of Alanine scan and N-methyl amide derivatives of Ac-bombesin[7-14]. Development of a proposed binding conformation at the neuromedin B (NMB) and gastrin releasing peptide (GRP) receptors](https://attachments.academia-assets.com/72929796/thumbnails/1.jpg)
](International Journal of Peptide and Protein Research, 1996
Alanine and N-methylation scans together with molecular modelling were implemented in order to pr... more Alanine and N-methylation scans together with molecular modelling were implemented in order to propose a binding conformation of the minimum active fragment of bombesin (BB), Ac-BB[7-141, to the gastrin releasing peptide (G R P) and neuromedin B (N M B) receptors. These data are also used to critically evaluate the previously proposed binding conformations such as ?-helix and antiparallel 8-sheets. This shows that the preciously reported conformations d o not satisfy the experimental data. A new binding conformation of Ac-BB[7-14] is proposed consisting of three consecutive y-turns followed by a bend and finishing with two ;#-turns. This low energy conformation (analogous to a fragment of thymidylate synthase, 2TSC) of bombesin stabilized by five internal hydrogen bonds, and with the side chains of residues Trp' and Leu" held on the same side of the peptide, is in agreement with the experimentally observed data. This and the results of molecular modelling may aid in the synthesis of conformationally restricted high affinity bombesin analogues and/or high affinity template-based GRP or NMB receptor agonists arid antagonists. Q Munksgaard 1996.
Trends in Pharmacological Sciences, 2000
The manner in which a cell responds to and influences its environment is ultimately determined by... more The manner in which a cell responds to and influences its environment is ultimately determined by the genes that it expresses. To fully understand and manipulate cellular function, identification of these expressed genes is essential. Techniques such as RT-PCR enable examination of gene expression at the tissue level. However, the study of complex heterogeneous tissue, such as the CNS or immune system, requires gene analysis to be performed at much higher resolution. In this article, the various methods that have been developed to enable RT-PCR to be performed at the level of the single cell are reviewed. In addition, how, when carried out in combination with techniques such as patchclamp recording, single-cell gene-expression studies extend our understanding of biological systems is discussed.
The Journal of Physiology, 2001
ABSTRACT
The Journal of Physiology, 2001
Voltage-gated sodium channels play an important role in excitable cells. They mediate an increase... more Voltage-gated sodium channels play an important role in excitable cells. They mediate an increase in Na + ion permeability thereby transmitting depolarising impulses rapidly throughout cells and cell networks (Catterall, 1984). These molecules are also thought to perform a pivotal role during CNS development since action potential propagation and excitatory transmission are vital in the maturation of neuronal morphological, electrophysiological and molecular properties (Shatz, 1990; Fields & Nelson, 1992; Goodman & Shatz, 1993). Although current evidence strongly supports the functional importance of sodium channels during development, little information presently exists concerning their molecular properties.
iv) ACKNOWLEDGEMENTS (v) ABBREVIATIONS ( CHAPTER ONE. INTRODUCTION 1. Substance P 1 1.1. Isolatio... more iv) ACKNOWLEDGEMENTS (v) ABBREVIATIONS ( CHAPTER ONE. INTRODUCTION 1. Substance P 1 1.1. Isolation and structure 1 1.2. Distribution of substance P in the brain 1 1.3. Structure activity studies in peripheral preparations 1 1.4. Structure activity relationships in the CNS 2 1.5. Metabolism of substance P 3 1.6. Mechanism of action 4 1.7. Possible role of substance P in the CNS 5 2. Melanocyte stimulating hormone release inhibitory factor (MIF) 8 2.1. General pharmacology of MIF 8 2.2. Interactions of MSH and MIF with dopamine 8 3 Thyrotropin releasing hormone (TRH) 12 3.1. General pharmacology of TRH 12 3.2. TRH in the CNS 12 k. Opioid peptides I6 4.1. Opioid peptides in the CNS 16 U.2. Interactions between dopamine and opiates I6 5. Dopamine 19 5.1. Dopamine, distribution and pathways in the CNS 19 5.2. Biochemistry of dopamine release, receptor binding and postsynaptic actions I9 5.3. lontophoretic dopamine pharmacology in the caudate nucleus and nucleus accumbens 20 5.4. Effect o...
Journal of Experimental Biology
N-Methyl lycaconitine is the most effective low molecular weight antagonist reported for an insec... more N-Methyl lycaconitine is the most effective low molecular weight antagonist reported for an insect neuronal nicotinic receptor. In the present study, the citrate salt of this neurotoxin from the plant Delphinium brownii was found to inhibit [3H]-α-bungarotoxin binding to nerve cord extracts of the cockroach Periplaneta americana with a Ki of l.4×10−9moll−1. At a concentration of 1.0×10−7moll−1, N-methyl lycaconitine completely blocked the response to ionophoretically applied acetylcholine recorded from the cell body membrane of the fast coxal depressor motor neurone (Df) in the desheathed metathoracic ganglion of the cockroach. The block was voltage-independent over the range of membrane potential −100 to −30 mV. The effectiveness of N-methyl lycaconitine on the nicotinic receptor, which is present in very high concentrations in the insect nervous system, suggests that this alkaloid is a natural plant protection agent.
Cell Calcium, Aug 1, 1998
In human U373 MG astrocytoma cells, histamine and substance P stimulated similar peak increases i... more In human U373 MG astrocytoma cells, histamine and substance P stimulated similar peak increases in intracellular free calcium concentrations ([Ca2+]i), as measured by single cell imaging of Fura-2 fluorescence. Best-fit EC50 values for the peak Ca2+ response were 1.86 microM for histamine and 0.93 nM for substance P. The histamine Ca2+ response was manifest as either a series of repetitive spikes, or, at higher concentrations, a peak followed by a lower plateau level of Ca2+. In contrast, the substance P response became more transient at higher agonist concentrations. Substance P (10 nM) stimulated a biphasic increase in levels of inositol (1,4,5) trisphosphate (Ins(1,4,5)P3) with a peak of 97 +/- 5 pmoles/mg protein at 10 s. In contrast, the Ins(1,4,5)P3 response to 100 microM histamine was only marginally above basal levels of around 12 pmoles/mg protein. However, concentrations of histamine and substance P giving similar Ins(1,4,5)P3 responses produce similar peak increases in [Ca2+]i. HPLC analysis indicated that histamine stimulated the production of [3H]-Ins(1,4,5)P3 and its metabolites, although the magnitude of response was smaller than that observed with substance P. The initial Ca2+ responses to histamine and substance P did not require the presence of extracellular Ca2+. The Ca2+ response to histamine was unaffected by treatment with ryanodine, and was shifted to areas of lower agonist concentration by thimerosal. These results demonstrate that extremely small increases in Ins(1,4,5)P3 can stimulate large increases in [Ca2+]i in U373 MG cells, and suggest a marked redundancy for Ins(1,4,5)P3 production in the Ca2+ signalling pathway.
Pflugers Arch Eur J Physiol, 2001
Hypertrophy is an adaptive response of the heart to myocardial injury or hemodynamic overload tha... more Hypertrophy is an adaptive response of the heart to myocardial injury or hemodynamic overload that may progress and contribute to cardiac decompensation and eventually to heart failure. The signaling pathways controlling this response in the cardiac myocyte are poorly understood. A data mining effort of a human failed heart cDNA library was undertaken in an effort to identify novel signaling molecules involved in cardiac hypertrophy. This effort identified a novel kinase (MLK7) homologous to the mixed lineage kinase family of proteins. The mixed lineage kinases are mitogenactivated protein kinase kinase kinases (MAPKKKs) which activate stress activated protein kinase/c-Jun Nterminal kinase (SAPK/JNK) and p38 kinase pathways. They contain a catalytic domain with homology to both serine/threonine and tyrosine-specific kinases and a dual leucine zipper. MLK7 is identical to leucine zipper and sterile-alpha motif protein kinase (ZAK) through the leucine zipper domain but has a completely divergent COOH-terminus and shares approximately 40% homology with the other MLKs overall. Expression of MLK7 mRNA is most abundant in skeletal muscle and heart, with expression restricted to the cardiac myocyte. The recombinant histidine tagged MLK7 expressed and purified from insect cells exhibited serine/ threonine kinase activity in vitro with myelin basic protein as substrate. When expressed in cardiac myocytes, MLK7 activated SAPK/JNK1, and ERK and p38 to a lesser extent. Additionally, MLK7 altered fetal gene expression and increased protein synthesis in cardiac myocytes. These data suggest that MLK7 is a new member of the mixed lineage kinase family that modulates cardiac SAPK/JNK pathway and may play a role in cardiac hypertrophy and progression to heart failure.
Neuropharmacology, 1983
Neurones in the substantia nigra were found to be sensitive to iontophoretically applied substanc... more Neurones in the substantia nigra were found to be sensitive to iontophoretically applied substance P, substance P 1-9 methyl ester and substance P 1-9 amide. Substance P 1-2, 4-9 and 5-9 methyl esters, thyrotropin releasing hormone (TRH), Pyroglutamyl-histidyl-2 methyl prolineamide (methyl TRH), Pyroglutamyl-histidyl-2 methyl prolineamide (methyl TRH), histidyl-proline-diketopiperazine (His-Pro) and MSH releasing inhibiting factor (MIF) were without effect on neurones in this area. Thyrotropin releasing hormone (TRH), methyl TRH, His-Pro and MIF were inactive on neurones in the caudate nucleus and nucleus accumbens. Bilateral injections of substance P and substance P 1-9 methyl ester into the ventral tegmental area (VTA) of conscious rats produced locomotor activity, while similar injections of substance P 4-9 and 5-9 methyl esters did not. The locomotor activity produced by amphetamine was prolonged by TRH, while MIF was devoid of such activity. The data suggest that substance P an...
The Journal of physiology, 1991
1. The effects on dorsal raphe neurones of the peptides bombesin, gastrin-releasing peptide and n... more 1. The effects on dorsal raphe neurones of the peptides bombesin, gastrin-releasing peptide and neuromedin B were studied using intracellular recording techniques from slices of rat brain maintained in vitro. The peptides were added to the solutions perfusing the slices. 2. The peptides bombesin, gastrin-releasing peptide and neuromedin B depolarized neurones in the dorsal raphe nucleus. The same neurones were depolarized by phenylephrine and hyperpolarized by 5-hydroxytryptamine (5-HT) but were insensitive to sulphated cholecystokinin octapeptide (CCK). 3. The responses to the peptides were not blocked by CCKA, CCKB and alpha 1-adrenoreceptor antagonists. 4. The response to the peptides persisted in the presence of tetrodotoxin (TTX) and low-calcium, high-magnesium-containing artificial cerebrospinal fluid (ACSF). 5. Under voltage clamp conditions the peptides caused a decrease in membrane conductance accompanied by an inward current. The reversal potential for the event was the sa...
Neuropharmacology, 2002
We have used the whole cell patch clamp method and fura-2 fluorescence imaging to study the actio... more We have used the whole cell patch clamp method and fura-2 fluorescence imaging to study the actions of gabapentin (1-(aminoethyl) cyclohexane acetic acid) on voltage-activated Ca(2+) entry into neonatal cultured dorsal root ganglion (DRG) neurones and differentiated F-11 (embryonic rat DRG x neuroblastoma hybrid) cells. Gabapentin (2.5 microM) in contrast to GABA (10 microM) did not influence resting membrane potential or input resistance. In current clamp mode gabapentin failed to influence the properties of evoked single action potentials but did reduce the duration of action potentials prolonged by Ba(2+). Gabapentin attenuated high voltage-activated Ca(2+) channel currents in a dose- and voltage- dependent manner in DRG neurones and reduced Ca(2+) influx evoked by K(+) depolarisation in differentiated F-11 cells loaded with fura-2. The sensitivity of DRG neurones to gabapentin was not changed by the GABA(B) receptor antagonist saclofen but pertussis toxin pre-treatment reduced t...
Molecular pharmacology, 1999
Although activation of G protein-coupled inward rectifying K+ (GIRK) channels by Gi/Go-coupled re... more Although activation of G protein-coupled inward rectifying K+ (GIRK) channels by Gi/Go-coupled receptors has been shown to be important in postsynaptic inhibition in the central nervous system, there is also evidence to suggest that inhibition of GIRK channels by Gq-coupled receptors is involved in postsynaptic excitation. In the present study we addressed whether the Gq-coupled receptors of the bombesin family can couple to GIRK channels and examined the mechanism by which this process occurs. Different combinations of GIRK channel subunits (Kir3.1, Kir3.2, and Kir3.4) and bombesin receptors (BB1 and BB2) were expressed in Xenopus oocytes. In all combinations tested GIRK currents were reversibly inhibited upon application of the bombesin-related peptides, neuromedin B or gastrin-releasing peptide in a concentration-dependent manner. Incubation of oocytes in the phospholipase C inhibitor U73122 or the protein kinase C (PKC) inhibitors chelerythrine and staurosporine significantly re...
International Journal of Peptide and Protein Research, 1996
Alanine and N-methylation scans together with molecular modelling were implemented in order to pr... more Alanine and N-methylation scans together with molecular modelling were implemented in order to propose a binding conformation of the minimum active fragment of bombesin (BB), Ac-BB[7-141, to the gastrin releasing peptide (G R P) and neuromedin B (N M B) receptors. These data are also used to critically evaluate the previously proposed binding conformations such as ?-helix and antiparallel 8-sheets. This shows that the preciously reported conformations d o not satisfy the experimental data. A new binding conformation of Ac-BB[7-14] is proposed consisting of three consecutive y-turns followed by a bend and finishing with two ;#-turns. This low energy conformation (analogous to a fragment of thymidylate synthase, 2TSC) of bombesin stabilized by five internal hydrogen bonds, and with the side chains of residues Trp' and Leu" held on the same side of the peptide, is in agreement with the experimentally observed data. This and the results of molecular modelling may aid in the synthesis of conformationally restricted high affinity bombesin analogues and/or high affinity template-based GRP or NMB receptor agonists arid antagonists. Q Munksgaard 1996.
Trends in Pharmacological Sciences, 2000
The manner in which a cell responds to and influences its environment is ultimately determined by... more The manner in which a cell responds to and influences its environment is ultimately determined by the genes that it expresses. To fully understand and manipulate cellular function, identification of these expressed genes is essential. Techniques such as RT-PCR enable examination of gene expression at the tissue level. However, the study of complex heterogeneous tissue, such as the CNS or immune system, requires gene analysis to be performed at much higher resolution. In this article, the various methods that have been developed to enable RT-PCR to be performed at the level of the single cell are reviewed. In addition, how, when carried out in combination with techniques such as patchclamp recording, single-cell gene-expression studies extend our understanding of biological systems is discussed.
The Journal of Physiology, 2001
ABSTRACT
The Journal of Physiology, 2001
Voltage-gated sodium channels play an important role in excitable cells. They mediate an increase... more Voltage-gated sodium channels play an important role in excitable cells. They mediate an increase in Na + ion permeability thereby transmitting depolarising impulses rapidly throughout cells and cell networks (Catterall, 1984). These molecules are also thought to perform a pivotal role during CNS development since action potential propagation and excitatory transmission are vital in the maturation of neuronal morphological, electrophysiological and molecular properties (Shatz, 1990; Fields & Nelson, 1992; Goodman & Shatz, 1993). Although current evidence strongly supports the functional importance of sodium channels during development, little information presently exists concerning their molecular properties.