Identification of ionic currents at presynaptic nerve endings of the lizard.

1. Ionic currents associated with the invasion of an action potential into the motor nerve ending of the lizard, Anolis carolinensis, were measured with a focal extracellular electrode at several locations along the nerve ending. 2. These experimentally observed currents could be matched with computer simulations of action potential propagation into the nerve ending. They revealed that while Na+ channels are the major ionic current pathway in the heminode, K+ channels provide the major pathway in the terminal branches and boutons. 3. Calcium current in the presynaptic ending was unmasked by the application of tetraethylammonium (TEA). This current was blocked by: (a) cadmium, (b) omega‐conotoxin GVIA and (c) nifedipine, but was unaffected by nickel at concentrations less than or equal to 100 microM. Nifedipine's action became more definitive when the duration of the action potential was greatly extended by pre‐treatment with TEA. The effect of Bay K 8644 was inconsistent. 4. Transmitter release, as measured by postsynaptic current, had a pharmacological response profile similar to that of the Ca2+ current, with the exception that transmitter release was increased reliably and reversibly by Bay K 8644. 5. This pharmacological response profile is identical to that of the L type Ca2+ channel identified by Fox, Nowycky & Tsien (1987 alpha) in chick dorsal root ganglion neurones. We saw no evidence for more than a single type of Ca2+ channel in lizard motor nerve endings. 6. A calcium‐activated K+ current IK(Ca) was revealed by application of 3,4‐diaminopyridine (DAP), a delayed‐rectifier K+ channel blocker. This K(Ca) current was blocked by TEA, charybdotoxin and by substitution of cobalt for extracellular calcium.

[1]  R. Tsien,et al.  Mechanism of calcium channel blockade by verapamil, D600, diltiazem and nitrendipine in single dialysed heart cells , 1983, Nature.

[2]  G. Dayanithi,et al.  Hormone release from isolated nerve endings of the rat neurohypophysis. , 1987, The Journal of physiology.

[3]  M H Brill,et al.  Conduction through demyelinated plaques in multiple sclerosis: computer simulations of facilitation by short internodes. , 1978, Journal of neurology, neurosurgery, and psychiatry.

[4]  R. Latorre,et al.  Charybdotoxin, a protein inhibitor of single Ca2+-activated K+ channels from mammalian skeletal muscle , 1985, Nature.

[5]  E. F. Stanley,et al.  A model for exocytosis based on the opening of calcium-activated potassium channels in vesicles. , 1985, Life sciences.

[6]  M. Sanguinetti,et al.  Voltage-dependent modulation of Ca channel current in heart cells by Bay K8644 , 1986, The Journal of general physiology.

[7]  S. M. Goldin,et al.  Calcium channels in rat brain synaptosomes: identification and pharmacological characterization. High affinity blockade by organic Ca2+ channel blockers , 1985, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[8]  B. Katz,et al.  Propagation of electric activity in motor nerve terminals , 1965, Proceedings of the Royal Society of London. Series B. Biological Sciences.

[9]  R. Kream,et al.  Characterization of the electrically evoked release of substance P from dorsal root ganglion neurons: methods and dihydropyridine sensitivity , 1988, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[10]  R. Tsien,et al.  Omega-conotoxin: direct and persistent blockade of specific types of calcium channels in neurons but not muscle. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[11]  D. Middlemiss,et al.  A functional correlate for the dihydropyridine binding site in rat brain , 1985, Nature.

[12]  R. J. Miller,et al.  Multiple calcium channels and neuronal function. , 1987, Science.

[13]  C. Patte,et al.  Involvement of DHP voltage-sensitive calcium channels and protein kinase C in thyroliberin (TRH) release by developing hypothalamic neurons in culture , 1988, Brain Research.

[14]  F S Cohen,et al.  Osmotic swelling of vesicles: its role in the fusion of vesicles with planar phospholipid bilayer membranes and its possible role in exocytosis. , 1986, Annual review of physiology.

[15]  S. J. Smith,et al.  Calcium action in synaptic transmitter release. , 1987, Annual review of neuroscience.

[16]  M. Nowycky,et al.  Kinetic and pharmacological properties distinguishing three types of calcium currents in chick sensory neurones. , 1987, The Journal of physiology.

[17]  P. M. Hinkle,et al.  Dihydropyridine Ca2+ antagonists: potent inhibitors of secretion from normal and transformed pituitary cells. , 1985, The American journal of physiology.

[18]  M. Nowycky,et al.  Single‐channel recordings of three types of calcium channels in chick sensory neurones. , 1987, The Journal of physiology.

[19]  D. Yoshikami,et al.  A venom peptide with a novel presynaptic blocking action , 1984, Nature.

[20]  B. Hille.  The Selective Inhibition of Delayed Potassium Currents in Nerve by Tetraethylammonium Ion , 1967, The Journal of general physiology.

[21]  A. Hodgkin.  Evidence for electrical transmission in nerve , 1937, The Journal of physiology.

[22]  Mark Ellisman,et al.  Studies of excitable membranes. II. A comparison of specializations at neuromuscular junctions and nonjunctional sarcolemmas of mammalian fast and slow twitch muscle fibers , 1976, The Journal of cell biology.

[23]  T. Maéno,et al.  Effects of synthetic omega-conotoxin, a new type Ca2+ antagonist, on frog and mouse neuromuscular transmission. , 1987, European journal of pharmacology.

[24]  S G Waxman,et al.  Organization of ion channels in the myelinated nerve fiber. , 1985, Science.

[25]  T. Perney,et al.  Multiple calcium channels mediate neurotransmitter release from peripheral neurons. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[26]  E. Barrett,et al.  Effects of tetraethylammonium on the depolarizing after‐potential and passive properties of lizard myelinated axons. , 1988, The Journal of physiology.

[27]  W. Kennedy,et al.  Dimensions of myelinated nerve fibers near the motor and sensory terminals in cat tenuissimus muscles , 1979, Neuroscience.

[28]  J W Moore,et al.  Simulations of conduction in uniform myelinated fibers. Relative sensitivity to changes in nodal and internodal parameters. , 1978, Biophysical journal.

[29]  A. Peres,et al.  Computer reconstruction of the spread of excitation in nerve terminals with inhomogeneous channel distribution , 1986, European Biophysics Journal.

[30]  U. Proske,et al.  Histological and electrophysiological investigation of lizard skeletal muscle , 1968, The Journal of physiology.

[31]  Nerve impulse conduction from the myelinated portion of the axon to the nonmyelinated terminal , 1973 .

[32]  M Hines,et al.  A program for simulation of nerve equations with branching geometries. , 1989, International journal of bio-medical computing.

[33]  A. Mallart.  A calcium‐activated potassium current in motor nerve terminals of the mouse. , 1985, The Journal of physiology.

[34]  E. Barrett,et al.  Intracellular recording from vertebrate myelinated axons: mechanism of the depolarizing afterpotential , 1982, The Journal of physiology.

[35]  A. Hodgkin,et al.  A quantitative description of membrane current and its application to conduction and excitation in nerve , 1952, The Journal of physiology.

[36]  F. Segal,et al.  A CHARACTERIZATION OF FIBRANT SEGAL CATEGORIES , 2006, math/0603400.

[37]  R. Miller,et al.  Nerve growth factor modulates the drug sensitivity of neurotransmitter release from PC-12 cells. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[38]  T. Konishi.  Electrical excitability of motor nerve terminals in the mouse. , 1985, The Journal of physiology.

[39]  W. Atchison,et al.  Bay K 8644 increases release of acetylcholine at the murine neuromuscular junction , 1987, Brain Research.

[40]  J. Walrond,et al.  Structure of axon terminals and active zones at synapses on lizard twitch and tonic muscle fibers , 1985, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[41]  A. Ogura,et al.  Differential effect of a dihydropyridine derivative to Ca2+ entry pathways in neuronal preparations , 1984, Brain Research.

[42]  R. Horn,et al.  Role of calcium‐activated potassium channels in transmitter release at the squid giant synapse. , 1988, The Journal of physiology.

[43]  M. Sanguinetti,et al.  Voltage‐Dependent Block of Calcium Channel Current in the Calf Cardiac Purkinje Fiber by Dihydropyridine Calcium Channel Antagonists , 1984, Circulation research.

[44]  W R Gray,et al.  Peptide neurotoxins from fish-hunting cone snails. , 1985, Science.

[45]  C. Armstrong,et al.  Anomalous Rectification in the Squid Giant Axon Injected with Tetraethylammonium Chloride , 1965, The Journal of general physiology.

[46]  J. Woodward,et al.  Bay K 8644 stimulation of calcium entry and endogenous dopamine release in rat striatal synaptosomes antagonized by nimodipine , 1986, Brain Research.

[47]  A. Hodgkin.  Evidence for electrical transmission in nerve , 1937 .

[48]  佐野 和也.  Effects of synthetic ω-conotoxin, a new type Ca[2+] antagonist, on frog and mouse neuromuscular transmission , 1988 .

[49]  R. Miller,et al.  The effects of dihydropyridines on neurotransmitter release from cultured neuronal cells. , 1984, Life sciences.

[50]  R. Tsien,et al.  Dominant role of N-type Ca2+ channels in evoked release of norepinephrine from sympathetic neurons. , 1988, Science.

[51]  Mark Ellisman,et al.  STUDIES OF EXCITABLE MEMBRANES , 1974, The Journal of cell biology.

[52]  A. Mallart,et al.  Presynaptic currents in mouse motor endings , 1982, The Journal of physiology.

[53]  T. Narahashi,et al.  3,4-diaminopyridine. A potent new potassium channel blocker. , 1978, Biophysical journal.

[54]  A. Harvey,et al.  Effects of charybdotoxin, a blocker of Ca2+ ‐activated K + channels, on motor nerve terminals , 1988, British journal of pharmacology.

[55]  A. Hodgkin.  Evidence for electrical transmission in nerve: Part I. , 1937, The Journal of physiology.