Separation and modulation of calcium currents in bullfrog sympathetic neurons

The calcium current of frog sympathetic neurons has relatively rapid activation kinetics (tau < 3 ms) in response to changes in voltage. Pharmacologically, the current is blocked approximately 90% of omega-conotoxin, but < 10% by dihydropyridine antagonists. This suggests that nearly all of the current is N type. However, inactivation is slow and incomplete even for depolarizations lasting > 1 s, consistent with recent evidence that N-type channels do not always inactivate rapidly. The calcium current is partially inhibited via receptors for acetylcholine, luteinizing hormone releasing hormone, substance P, ATP, and norepinephrine. These effects are mimicked by internal dialysis with GTP-gamma-S, suggesting involvement of a G protein. The transmitters affect the activation kinetics of the calcium current in a voltage-dependent manner, which can be modeled as a reversible shift of some channels to "reluctant" states in which strong depolarization is needed to produce channel opening. The effects of transmitters develop and recover with t1/2 approximately 1-2 s, so if a second messenger is involved in receptor-calcium channel coupling, it must act rapidly.