Pharmacologically distinct presynaptic calcium channels in cerebellar excitatory and inhibitory synapses.
We have used whole-cell patch clamp recordings and pharmacological blockers of Ca channels to compare the pharmacology of Ca channels that mediate synaptic transmission at the three types of synapses innervating Purkinje cells in rat cerebellar slices. Both parallel fiber and climbing fiber excitatory synapses were sensitive to the P-type Ca channel blocker, omega-AgaIVA and the P/Q/N-type channel blocker, omega-conotoxin MVIIC. Transmission at inhibitory interneuronal synapses was not suppressed by these toxins, or by the N-type (omega-conotoxins GVIA and MVIIA) or L-type (nimodipine) channel blockers. Inhibitory transmission could be inhibited by Ni2+ and amiloride, but only at concentrations (IC50 approximately 300 microM) that affect other types of Ca channels. These results indicate that excitatory and inhibitory presynaptic terminals of the cerebellar cortex possess different types of voltage-gated Ca channels. The excitatory terminals contain P-type, Q-type and N-type Ca channels, with P-type channels playing the most prominent role. The inhibitory terminals possess quite different type(s) of Ca channel. The heterogeneous distribution of Ca channel types should impart unique properties to transmitter release from the excitatory and inhibitory terminals.
Doroshenko
P A
PA
Department of Neurobiology, Duke University Medical Center, Durham, NC 27710, USA. petrod@civich.ottawa.on.ca
Woppmann
A
A
Miljanich
G
G
Augustine
G J
GJ
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects* / Q000502:physiology; D002531:Cerebellum / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D018408:Patch-Clamp Techniques; D010455:Peptides / Q000494:pharmacology; D017729:Presynaptic Terminals / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013111:Spider Venoms / Q000494:pharmacology; D013569:Synapses / Q000187:drug effects*; D009435:Synaptic Transmission / Q000187:drug effects*; D020867:omega-Agatoxin IVA; D020960:omega-Conotoxins
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D010455:Peptides; D013111:Spider Venoms; D020867:omega-Agatoxin IVA; D020960:omega-Conotoxins; C075851:omega-conotoxin-MVIIC