Ca2+ channels that activate Ca2+-dependent K+ currents in neostriatal neurons

It is demonstrated that not all voltage-gated calcium channel types express ed in neostriatal projection neurons (L, N, P, Q and R) contribute equally to the activation of calcium-dependent potassium currents. Previous work ma de clear that different calcium channel types contribute with a similar amo unt of current to whole-cell calcium current in neostriatal neurons. It has also been shown that spiny neurons posses both "big" and "small" types of calcium-dependent potassium currents and that activation of such currents r elies on calcium entry through voltage-gated calcium channels. In the prese nt work it was investigated whether all calcium channel types equally activ ate calcium-dependent potassium currents. Thus, the action of organic calci um channel antagonists was investigated on the calcium-activated outward cu rrent. Transient potassium currents were reduced by 4-aminopyridine and sod ium currents were blocked by tetrodotoxin. It was found that neither 30 nM omega-Agatoxin-TK, a blocker of P-type channels, nor 200 nM calciseptine or 5 mu M nitrendipine, blockers of L-type channels, were able to significant ly reduce the outward current. In contrast, 400 nM omega-Agatoxin-TK, which at this concentration is able to block Q-type channels, and 1 mu M omega-C onotoxin GVIA, a blocker of N-type channels, both reduced outward current b y about 50%. These antagonists given together, or 500 nM omega-Conotoxin MW C, a blocker of N- and P/Q-type channels, reduced outward current by 70%. I n addition, the N- and P/Q-type channel blockers preferentially reduce the afterhyperpolarization recorded intracellularly. The results show that calcium-dependent potassium channels in neostriatal n eurons are preferentially activated by calcium entry through N- and Q-type channels in these conditions. (C) 1999 IBRO. Published by Elsevier Science Ltd.