N- and L- but not P/Q-type calcium channels contribute to neuropeptide release from rat skin in vitro.

Here we directly demonstrate the liberation of CGRP from rat skin in vitro induced by high extracellular concentrations of KCl. The EC50 was 52 mM KCl and saturation was reached from 80 mM KCl. The release was entirely dependent on the presence of extracellular calcium ions. It was reduced by nonsubtype selective inhibition of voltage-operated calcium channels (VOCCs). Application of selective antagonists suggest expression of L-type and N-type but not P/Q-type VOCCs in cutaneous nociceptive terminals. These may be activated by any suprathreshold depolarizing stimuli to induce neurogenic inflammation. The expression pattern greatly differs from central nociceptive terminals where, in addition, P/Q-type VOCC have been found.