It is demonstrated that not all
voltage-
gated calcium
channel types expressed in neostriatal projection neurons (L, N, P, Q and R) contribute equally to the activation of calcium-dependent
potassium currents. Previous work made clear that different calcium
channel types contribute with a similar amount 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 relies on calcium entry through
voltage-
gated calcium
channels. In the present work it was investi
gated whether all calcium
channel types equally activate calcium-dependent
potassium currents. Thus, the action of organic calcium
channel antagonists was investi
gated on the calcium-activated outward current. Transient
potassium currents were reduced by 4-aminopyridine and sodium currents were blocked by tetrodotoxin. It was found that neither 30 nM ω-Agatoxin-TK, a blocker of P-type
channels, nor 200 nM calciseptine or 5 μM nitrendipine, blockers of L-type
channels, were able to significantly reduce the outward current. In contrast, 400 nM ω-Agatoxin-TK, which at this concentration is able to block Q-type
channels, and 1 μM ω-Conotoxin GVIA, a blocker of N-type
channels, both reduced outward current by about 50 % . These antagonists given together, or 500 nM ω-Conotoxin MVIIC, a blocker of N- and P/Q-type
channels, reduced outward current by 70 % . In 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 neurons are preferentially activated by calcium entry through N- and Q-type channels in these conditions.