K+-STIMULATED CA-45(2+) FLUX INTO RAT NEOCORTICAL MINI-SLICES IS BLOCKED BY OMEGA-AGA-IVA AND THE DUAL NA+/CA2+ CHANNEL BLOCKERS LIDOFLAZINE AND FLUNARIZINE

High-threshold neuronal voltage-sensitive Ca2+ channels (VSCCs) have been classified into at least three subtypes, including L, N, and P, based on biophysical and pharmacological criteria. We examined K+-induced Ca-45(2+) flux into rat neocortical mini-slices to determine which of these subtype(s) might be involved in this phenomenon. Neither the L-type Ca2+ channel antagonist isradipine at 10 muM nor the N-type antagonist omega-conotoxin GVIA at 1 muM were effective antagonists of Ca-45(2+) flux in this model. However, the P-type Ca2+ channel antagonist, omega-Aga-IVA, blocked 70% of flux at 200 nM, with an IC50 of 17 nM, strongly implicating P-type Ca2+ channel involvement in K+-stimulated Ca2+ entry into mammalian nerve terminals. About 30% of the flux response was resistant to the action of omega-Aga-IVA, suggesting that a still uncharacterized subtype of VSCC is involved in Ca2+ entry into mammalian nerve terminals. Both the omega-Aga-IVA sensitive and insensitive components of Ca-45(2+) flux were blocked by the diphenylalkylpiperazines, lidoflazine and flunarizine (IC50 = 6.4 muM and 11 muM, respectively), which have dual Na+/Ca2+ channel blocking actions.