Nonuniform distribution of Ca2+ channel subtypes on presynaptic terminals of excitatory synapses in hippocampal cultures.
Several subtypes of Ca2+ channel support the release of glutamate at excitatory synapses. We investigated the pattern of colocalization of these subtypes on presynaptic terminals in hippocampal cultures. N-type (conotoxin GVIA-sensitive) or P/Q-type (agatoxin IVA-sensitive) Ca2+ channels were blocked selectively, and the reduction in transmitter release probability (Pr) was measured with MK-801. The antagonists completely blocked release at some terminals, reduced Pr at others, and failed to affect the remainder. In contrast, nonselective reduction of presynaptic Ca2+ influx by adding Cd2+ or lowering external Ca2+ reduced Pr uniformly at all terminals. We conclude from these results that the mixture of N-type and P/Q-type channels varies markedly between terminals on the same afferent. The distribution of Ca2+ channel subtypes was the same for high and low Pr terminals. Given that Ca2+ channel subtypes are affected differentially by neuromodulators, these findings lead to the possibility of terminal-specific modulation of synaptic function.
Reid
C A
CA
Division of Neuroscience, John Curtin School of Medical Research, Australian National University, Canberra, ACT 2601, Australia.
Clements
J D
JD
Bekkers
J M
JM
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000145:classification* / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D016291:Dizocilpine Maleate / Q000494:pharmacology; D005071:Evoked Potentials / Q000187:drug effects; D006624:Hippocampus / Q000502:physiology*; D007700:Kinetics; D008959:Models, Neurological; D016202:N-Methylaspartate / Q000494:pharmacology; D009474:Neurons / Q000502:physiology*; D010455:Peptides / Q000494:pharmacology; D017729:Presynaptic Terminals / Q000187:drug effects / Q000502:physiology*; D013111:Spider Venoms / Q000494:pharmacology; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D020867:omega-Agatoxin IVA; D020866:omega-Conotoxin GVIA
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D010455:Peptides; D013111:Spider Venoms; D020867:omega-Agatoxin IVA; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate; D020866:omega-Conotoxin GVIA