Pharmacological and biophysical properties of Ca2+ channels and subtype distributions in human adrenal chromaffin cells

Abstract

In this study, we explored the pharmacological and biophysical properties of voltage-activated Ca2+ channels in human chromaffin cells using the perforated-patch configuration of the patch-clamp technique. According to their pharmacological sensitivity to Ca2+ channel blockers, cells could be sorted into two groups of similar size showing the predominance of either N- or P/Q-type Ca2+ channels. R-type Ca2+ channels, blocked by 77% with 20 muM Cd2+ and not affected by 50 muM Ni2+, were detected for the first time in human chromaffin cells. Immunocytochemical experiments revealed an even distribution of alpha (1E) Ca2+ channels in these cells. With regard to their biophysical properties, L- and R-type channels were activated at membrane potentials that were 15-20 mV more negative than P/Q- and N-type channels. Activation time constants showed no variation with voltage for the L-type channels, decreased with increasing potentials for the R- and P/Q-type channels, and displayed a bell shape with a maximum at 0 mV for the N-type channels. R-type channels were also the most inactivated channels. We thus show here that human chromaffin cells possess all the Ca2+ channel types described in neurons, L, N, P/Q, and R channels, but the relative contributions of N and P/Q channels differ among cells. Given that N- and P/Q-type Ca2+ channel types can be differentially modulated, these findings suggest the possibility of cell-specific regulation in human chromaffin cells.