Participation of multiple calcium channel types in transmission at single climbing fiber to Purkinje cell synapses

The sensitivity of synaptic transmission to antagonists of different calcium channels was examined at the powerful climbing fiber synapse between neurons from the inferior olive and cerebellar Purkinje cells. In rat brain slices, climbing fibers were activated with extracellular electrodes, and synaptic currents were recorded with whole-cell patch clamp. Dihydropyridines did not discernibly affect synaptic strength. omega-Conotoxin GVIA, a potent antagonist of N-type calcium channels, reduced synaptic currents by an average of 29%. omega-Agatoxin-IVA, a high affinity blocker of P-type calcium channels, reduced synaptic strength by an average of 77%. Together, the two toxins virtually eliminated synaptic transmission (91% inhibition). These results indicate that omega-agatoxin-IVA-sensitive calcium channels play an important role in transmission at the climbing fiber synapse. They also suggest that in single climbing fibers, release is evoked by at least two pharmacologically distinct calcium currents, one sensitive to omega-agatoxin-IVA, the other to omega-conotoxin GVIA.

[1]  R. Tsien,et al.  Functional expression of a rapidly inactivating neuronal calcium channel , 1993, Nature.

[2]  W R Gray,et al.  Peptide toxins from venomous Conus snails. , 1988, Annual review of biochemistry.

[3]  A. Konnerth,et al.  Synaptic currents in cerebellar Purkinje cells. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[4]  K. Beam,et al.  Action potential waveform voltage-clamp commands reveal striking differences in calcium entry via low and high voltage activated calcium channels , 1991, Neuron.

[5]  J. Nakai,et al.  Primary structure and functional expression from complementary DNA of a brain calcium channel , 1991, Nature.

[6]  B. Bean,et al.  Block of calcium channels in rat neurons by synthetic ω-Aga-IVA , 1993, Neuropharmacology.

[7]  B. Bean,et al.  Classes of calcium channels in vertebrate cells. , 1989, Annual review of physiology.

[8]  J. Nakai,et al.  Primary structure and functional expression of the ω-conotoxin-sensitive N-type calcium channel from rabbit brain , 1993, Neuron.

[9]  G. Matthews,et al.  Calcium influx and calcium current in single synaptic terminals of goldfish retinal bipolar neurons. , 1992, The Journal of physiology.

[10]  J. Eccles,et al.  The excitatory synaptic action of climbing fibres on the Purkinje cells of the cerebellum , 1966, The Journal of physiology.

[11]  H. Lux,et al.  A low voltage-activated, fully inactivating Ca channel in vertebrate sensory neurones , 1984, Nature.

[12]  R. Miller,et al.  Voltage-sensitive Ca2+ channels. , 1992, The Journal of biological chemistry.

[13]  Michael E. Adams,et al.  P-type calcium channels in rat central and peripheral neurons , 1992, Neuron.

[14]  B. Bean,et al.  Ca2+ channels in rat central and peripheral neurons: High-threshold current resistant to dihydropyridine blockers and ω-conotoxin , 1991, Neuron.

[15]  Masao Ito,et al.  Climbing fibre induced depression of both mossy fibre responsiveness and glutamate sensitivity of cerebellar Purkinje cells , 1982, The Journal of physiology.

[16]  B. Katz,et al.  The timing of calcium action during neuromuscular transmission , 1967, The Journal of physiology.

[17]  P Hess,et al.  Calcium channels in vertebrate cells. , 1990, Annual review of neuroscience.

[18]  R. Tsien,et al.  Multiple types of neuronal calcium channels and their selective modulation , 1988, Trends in Neurosciences.

[19]  M. Adams,et al.  Calcium channels coupled to glutamate release identified by omega-Aga-IVA. , 1992, Science.

[20]  A. Konnerth,et al.  Synaptic‐ and agonist‐induced excitatory currents of Purkinje cells in rat cerebellar slices. , 1991, The Journal of physiology.

[21]  D. Logothetis,et al.  Elementary properties and pharmacological sensitivities of calcium channels in mammalian peripheral neurons , 1989, Neuron.

[22]  M. Adams,et al.  P-type calcium channels blocked by the spider toxin ω-Aga-IVA , 1992, Nature.

[23]  R. Llinás,et al.  P-type voltage-dependent calcium channel mediates presynaptic calcium influx and transmitter release in mammalian synapses. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[24]  B. Bean.  Pharmacology of calcium channels in cardiac muscle, vascular muscle, and neurons. , 1991, American journal of hypertension.

[25]  D. Triggle,et al.  1,4-Dihydropyridine activators and antagonists: structural and functional distinctions. , 1989, Trends in pharmacological sciences.

[26]  A. Momiyama,et al.  Different types of calcium channels mediate central synaptic transmission , 1993, Nature.

[27]  J. Kemp,et al.  The effect of ω‐conotoxin GVIA on synaptic transmission within the nucleus accumbens and hippocampus of the rat in vitro , 1991, British journal of pharmacology.

[28]  R. Tsien,et al.  Distinctive biophysical and pharmacological properties of class A (BI) calcium channel α 1 subunits , 1993, Neuron.

[29]  J. Luebke,et al.  Multiple calcium channel types control glutamatergic synaptic transmission in the hippocampus , 1993, Neuron.

[30]  H. Lux,et al.  Pharmacological characterization of calcium currents and synaptic transmission between thalamic neurons in vitro , 1992, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[31]  P. Dutar,et al.  Omega-conotoxin GVIA blocks synaptic transmission in the CA1 field of the hippocampus. , 1989, European journal of pharmacology.

[32]  U. Ruegg,et al.  Stereoselectivity at the Calcium Channel: Opposite Action of the Enantiomers of a 1,4‐Dihydropyridine , 1985, Journal of cardiovascular pharmacology.

[33]  S. Narumiya,et al.  Primary structure and functional expression of the cardiac dihydropyridine-sensitive calcium channel , 1989, Nature.

[34]  M. Williams,et al.  Structure and functional expression of an omega-conotoxin-sensitive human N-type calcium channel. , 1992, Science.

[35]  E. F. Stanley,et al.  Calcium currents recorded from a vertebrate presynaptic nerve terminal are resistant to the dihydropyridine nifedipine. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[36]  R Llinás,et al.  Blocking and isolation of a calcium channel from neurons in mammals and cephalopods utilizing a toxin fraction (FTX) from funnel-web spider poison. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[37]  S. Vincent,et al.  Structure and functional expression of a member of the low voltage-activated calcium channel family. , 1993, Science.

[38]  B M Salzberg,et al.  Calcium channels that are required for secretion from intact nerve terminals of vertebrates are sensitive to omega-conotoxin and relatively insensitive to dihydropyridines. Optical studies with and without voltage-sensitive dyes , 1989, The Journal of general physiology.

[39]  R. Llinás,et al.  Localization of P-type calcium channels in the central nervous system. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[40]  Jose R. Lemos,et al.  Two types of calcium channels coexist in peptide-releasing vertebrate nerve terminals , 1989, Neuron.

[41]  J W Moore,et al.  Identification of ionic currents at presynaptic nerve endings of the lizard. , 1989, The Journal of physiology.

[42]  A. Konnerth,et al.  Sodium action potentials in the dendrites of cerebellar Purkinje cells. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[43]  F. Dodge,et al.  Co‐operative action of calcium ions in transmitter release at the neuromuscular junction , 1967, The Journal of physiology.

[44]  P. Reiner,et al.  Ca2+ channels: diversity of form and function , 1992, Current Opinion in Neurobiology.

[45]  R. Llinás,et al.  Transmission by presynaptic spike-like depolarization in the squid giant synapse. , 1982, Proceedings of the National Academy of Sciences of the United States of America.

[46]  R. Tsien,et al.  Three types of neuronal calcium channel with different calcium agonist sensitivity , 1985, Nature.

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

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

[49]  D. Linden,et al.  Cellular mechanisms of long-term depression in the cerebellum , 1993, Current Opinion in Neurobiology.