Voltage-sensitive Ca2+ channels in rat striatal synaptosomes: role on the [Ca2+]i responses to membrane depolarization.
The fluorescent Ca2+ indicator Indo-1 was used to study the effect of depolarization evoked by KCl or 4-aminopyridine (4-AP) on the intracellular free calcium concentration responses (delta[Ca2+]i) in rat striatal synaptosomes. Depolarization of the synaptosomes with [KCl] > 7.5 mM induced a rapid increase of the [Ca2+]i followed by a decay towards a plateau. The size of the [Ca2+]i response varied sigmoidally with the synaptosomal membrane potential, with a transition potential of -27.3 mV. Depolarization with 4-AP evoked a dose-dependent sustained increase of the [Ca2+]i. Nitrendipine, omega-Conotoxin GVIA (omega-CgTx) and omega-Agatoxin IVA (omega-Aga IVA) were used to evaluate the relative role of L-, N-, P- and possibly Q-type voltage-sensitive Ca2+ channels (VSCCs) on the [Ca2+]i changes evoked by each of the two depolarizing agents. Nitrendipine caused only about 10% inhibition of the effect of either agent on the [Ca2+]i, suggesting that the L-type VSCCs have a modest contribution. The omega-CgTx decreased the response to KCl and 4-AP by 15 and 30%, respectively, but the latter effect may be partially due to a non-specific effect on Na+ channels. The omega-Aga IVA reduced the response to 4-AP by 26.5%, and this effect was additive to that of omega-CgTx, further suggesting that the striatal nerve terminals possess P- and/or Q-type, in addition to N-type Ca2+ channels. Neomycin (0.35 mM), tentatively used as an antagonist of the P-type channels, had a potent effect, decreasing the response to K(+)-depolarization and to 4-AP by, respectively, 32.5 and 48.5%. It is suggested that at the concentration used the antibiotic also partially blocks VSCCs which do not belong to the L-, N-, P- or Q-type VSCCs. We conclude that striatal nerve endings are equipped with at least four to five pharmacologically distinct classes of VSCCs, which are sensitive to well known antagonists of the L-, N-, P-, and Q-type VSCCs.
Duarte
C B
CB
Department of Zoology, University of Coimbra, Portugal.
Cristóvão
A J
AJ
Carvalho
A P
AP
Carvalho
C M
CM
D015761:4-Aminopyridine / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000502:physiology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D004594:Electrophysiology; D066298:In Vitro Techniques; D015640:Ion Channel Gating / Q000187:drug effects; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism*; D009411:Nerve Endings / Q000187:drug effects; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism*
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D011189:Potassium Chloride; D015761:4-Aminopyridine; D002118:Calcium