Spontaneous muscle action potentials are blocked by N-type and P/Q-calcium channels blockers in the rat spinal cord-muscle co-culture system

This study investigated the effects of the calcium channel blockers nicardipine, calcicludine, ω-conotoxin GVIA, ω-agatoxin IVA, SNX-482, and NiCl on spontaneous muscle action potential of a rat spinal cord-muscle co-culture system. Spontaneous muscle action potential of the innervated muscle cells was blocked by d-tubocurarine (1 μM), but was not significantly affected by the L-type channel blocker nicardipine (100 nM). The neuronal L-type calcium channel blocker, calcicludine (50 and 100 nM), also had no effect on the frequency of spontaneous muscle action potential. However, nicardipine (100 nM) and calcicludine (100 nM) significantly increased the amplitude of muscle action potential. Application of the N-type calcium channel blocker, ω-conotoxin GVIA (50 and 100 nM), and the P/Q-type calcium channel blocker, ω-agatoxin IVA (10, 30, 50, and 100 nM), blocked the frequency and amplitude of spontaneous muscle action potential of the spinal cord-muscle co-cultured cells. In contrast, spontaneous muscle action potential was not affected by the R-type calcium channel blockers SNX-482 (100 nM) or NiCl (500 nM). These results indicate that blockers of N- and P/Q-type voltage-dependent calcium channels inhibit transmitter release at neuromuscular junctions in the rat spinal cord-muscle co-culture system.