Pharmacological and biophysical properties of Ca2+ channels and subtype distributions in human adrenal chromaffin cells.
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.
Pérez-Alvarez
Alberto
A
Departamento de Farmacología y Terapéutica, Facultad de Medicina, Universidad Autónoma de Madrid, c/ Arzobispo Morcillo 4, 28029, Madrid, Spain.
Hernández-Vivanco
Alicia
A
Cano-Abad
María
M
Albillos
Almudena
A
D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects* / Q000502:physiology*; D020908:Calcium Channels, R-Type / Q000378:metabolism; D027682:Cation Transport Proteins / Q000378:metabolism; D002478:Cells, Cultured; D019439:Chromaffin Cells / Q000187:drug effects* / Q000502:physiology*; D004299:Dopamine beta-Hydroxylase / Q000378:metabolism; D004594:Electrophysiology; D006801:Humans; D007150:Immunohistochemistry; D018408:Patch-Clamp Techniques; D010625:Phenylethanolamine N-Methyltransferase / Q000378:metabolism
C423009:CACNA1E protein, human; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D020908:Calcium Channels, R-Type; D027682:Cation Transport Proteins; D004299:Dopamine beta-Hydroxylase; D010625:Phenylethanolamine N-Methyltransferase