Presynaptic Ca2+ channels: a functional patchwork

A key step in the release of neurotransmitter is the entry of Ca(2+) into the presynaptic terminal via voltage-activated Ca(2+) channels. N-type and P/Q-type Ca(2+) channels play a predominant role but, surprisingly, their distribution across presynaptic terminals lacks any apparent order. They form a patchwork: at some terminals only N-type channels contribute to transmitter release and in others only P/Q-type channels contribute, but in many terminals both sub-types are active. The physiological implications of this non-uniform distribution are starting to emerge. Recent studies reveal that G-protein-mediated depression of N-type channels is stronger than that of P/Q-type channels, whereas voltage-dependent relief of inhibition is more pronounced for P/Q-type channels. The patchwork distribution of Ca(2+) channel subtypes might therefore enable terminal-specific modulation of transmitter release, enhancing the power of synaptic processing.

[1]  A. Dolphin Mechanisms of modulation of voltage‐dependent calcium channels by G proteins , 1998, The Journal of physiology.

[2]  J. Noebels,et al.  Presynaptic Ca2+ Channels and Neurotransmitter Release at the Terminal of a Mouse Cortical Neuron , 2001, The Journal of Neuroscience.

[3]  S. Iwasaki,et al.  Developmental changes in calcium channel types mediating synaptic transmission in rat auditory brainstem , 1998, The Journal of physiology.

[4]  J. Bekkers,et al.  N- and P/Q-Type Ca2+ Channels Mediate Transmitter Release with a Similar Cooperativity at Rat Hippocampal Autapses , 1998, The Journal of Neuroscience.

[5]  S. Gasparini,et al.  Presynaptic R-Type Calcium Channels Contribute to Fast Excitatory Synaptic Transmission in the Rat Hippocampus , 2001, The Journal of Neuroscience.

[6]  W. Regehr,et al.  Calcium control of transmitter release at a cerebellar synapse , 1995, Neuron.

[7]  K. Mackie,et al.  Modulation of Ca2+ channels βγ G-protein py subunits , 1996, Nature.

[8]  W. Catterall,et al.  Requirement for the synaptic protein interaction site for reconstitution of synaptic transmission by P/Q-type calcium channels , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[9]  J. Spafford,et al.  Functional interactions between presynaptic calcium channels and the neurotransmitter release machinery , 2003, Current Opinion in Neurobiology.

[10]  Nils Brose,et al.  Differential Control of Vesicle Priming and Short-Term Plasticity by Munc13 Isoforms , 2002, Neuron.

[11]  A. Craig,et al.  Molecular heterogeneity of central synapses: afferent and target regulation , 2001, Nature Neuroscience.

[12]  R. Tsien,et al.  Roles of N-type and Q-type Ca2+ channels in supporting hippocampal synaptic transmission. , 1994, Science.

[13]  J. Magee,et al.  Somatic EPSP amplitude is independent of synapse location in hippocampal pyramidal neurons , 2000, Nature Neuroscience.

[14]  R. Shigemoto,et al.  Co-expression of Metabotropic Glutamate Receptor 7 and N-type Ca2+ Channels in Single Cerebrocortical Nerve Terminals of Adult Rats* , 2003, Journal of Biological Chemistry.

[15]  R.J. Miller,et al.  Developmental changes in presynaptic calcium channels coupled to glutamate release in cultured rat hippocampal neurons , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[16]  D. T. Yue,et al.  Differential Occurrence of Reluctant Openings in G-Protein–Inhibited N- and P/Q-Type Calcium Channels , 2000, The Journal of general physiology.

[17]  H. Beck,et al.  Functional Specialization of Presynaptic Cav2.3 Ca2+ Channels , 2003, Neuron.

[18]  T. Momiyama Parallel decrease in ω‐conotoxin‐sensitive transmission and dopamine‐induced inhibition at the striatal synapse of developing rats , 2003, The Journal of physiology.

[19]  R. Tsien,et al.  Changes in action potential duration alter reliance of excitatory synaptic transmission on multiple types of Ca2+ channels in rat hippocampus , 1996, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[20]  W. Catterall Structure and regulation of voltage-gated Ca2+ channels. , 2000, Annual review of cell and developmental biology.

[21]  R. Tsien,et al.  Nomenclature of Voltage-Gated Calcium Channels , 2000, Neuron.

[22]  B Sakmann,et al.  Calcium Channel Types with Distinct Presynaptic Localization Couple Differentially to Transmitter Release in Single Calyx-Type Synapses , 1999, The Journal of Neuroscience.

[23]  S. Jones,et al.  LHRH and GTP-gamma-S modify calcium current activation in bullfrog sympathetic neurons. , 1990, Neuron.

[24]  R. Malinow,et al.  The probability of transmitter release at a mammalian central synapse , 1993, Nature.

[25]  D. T. Yue,et al.  Bursts of action potential waveforms relieve G‐protein inhibition of recombinant P/Q‐type Ca2+ channels in HEK 293 cells. , 1997, The Journal of physiology.

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

[27]  N. Akaike,et al.  Calcium channel subtypes on single GABAergic presynaptic terminal projecting to rat hippocampal neurons , 2002, Brain Research.

[28]  D. Brody,et al.  Relief of G-Protein Inhibition of Calcium Channels and Short-Term Synaptic Facilitation in Cultured Hippocampal Neurons , 2000, The Journal of Neuroscience.

[29]  B. Gähwiler,et al.  Either N- or P-type Calcium Channels Mediate GABA Release at Distinct Hippocampal Inhibitory Synapses , 1997, Neuron.

[30]  R. Shigemoto,et al.  Subtype-specific Expression of Group III Metabotropic Glutamate Receptors and Ca2+ Channels in Single Nerve Terminals* , 2002, The Journal of Biological Chemistry.

[31]  T. Snutch,et al.  Modulation of voltage-dependent calcium channels by G proteins , 1998, Current Opinion in Neurobiology.

[32]  B. Sakmann,et al.  Transmitter release modulation by intracellular Ca2+ buffers in facilitating and depressing nerve terminals of pyramidal cells in layer 2/3 of the rat neocortex indicates a target cell‐specific difference in presynaptic calcium dynamics , 2001, The Journal of physiology.

[33]  H. Reuter,et al.  Measurements of exocytosis from single presynaptic nerve terminals reveal heterogeneous inhibition by Ca2+-channel blockers , 1995, Neuron.

[34]  S. Kaech,et al.  Two Distinct Mechanisms Target Membrane Proteins to the Axonal Surface , 2003, Neuron.

[35]  W. Catterall,et al.  Subtype-selective reconstitution of synaptic transmission in sympathetic ganglion neurons by expression of exogenous calcium channels , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[36]  P. Saggau,et al.  Pharmacological identification of two types of presynaptic voltage- dependent calcium channels at CA3-CA1 synapses of the hippocampus , 1994, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[37]  Gail Mandel,et al.  Nomenclature of Voltage-Gated Sodium Channels , 2000, Neuron.

[38]  B. Gähwiler,et al.  Target cell-specific modulation of transmitter release at terminals from a single axon. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[39]  T. Südhof,et al.  α-Neurexins couple Ca2+ channels to synaptic vesicle exocytosis , 2003, Nature.

[40]  I. Bezprozvanny,et al.  Synaptic Targeting of N-Type Calcium Channels in Hippocampal Neurons , 2002, The Journal of Neuroscience.

[41]  S. W. Jones,et al.  LHRH and GTP-γ-S modify calcium current activation in bullfrog sympathetic neurons , 1990, Neuron.

[42]  R. Miller,et al.  Presynaptic inhibition at excitatory hippocampal synapses: development and role of presynaptic Ca2+ channels. , 1996, Journal of neurophysiology.

[43]  J. Bekkers,et al.  Nonuniform Distribution of Ca2+ Channel Subtypes on Presynaptic Terminals of Excitatory Synapses in Hippocampal Cultures , 1997, The Journal of Neuroscience.

[44]  H. Atwood,et al.  Diversification of synaptic strength: presynaptic elements , 2002, Nature Reviews Neuroscience.

[45]  S. Ikeda Voltage-dependent modulation of N-type calcium channels by G-protein β γsubunits , 1996, Nature.

[46]  A. Fox,et al.  Comparison of N- and P/Q-Type Voltage-Gated Calcium Channel Current Inhibition , 1997, The Journal of Neuroscience.

[47]  W. Shen,et al.  Presynaptic muscarinic inhibition in bullfrog sympathetic ganglia. , 1996, The Journal of physiology.

[48]  Christian Rosenmund,et al.  Nonuniform probability of glutamate release at a hippocampal synapse. , 1993, Science.

[49]  A. Momiyama,et al.  Developmental Changes in Calcium Channel Types Mediating Central Synaptic Transmission , 2000, The Journal of Neuroscience.

[50]  I. Mellman,et al.  Neuronal Polarity Controlling the Sorting and Diffusion of Membrane Components , 1999, Neuron.

[51]  A. Fox,et al.  Differential facilitation of N‐ and P/Q‐type calcium channels during trains of action potential‐like waveforms , 2002, The Journal of physiology.