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.

Human nicotinic receptors in chromaffin cells: characterization and pharmacology

“…In humans, chromaffin cells have an adrenergic phenotype (30) and they are the primary source for adrenaline production and release. In the human adrenal gland there is a juxtaposition of medulla and cortex (Fig.…”

Calcium entry through slow-inactivating L-type calcium channels preferentially triggers endocytosis rather than exocytosis in bovine chromaffin cells

“…The present study was planned to explore the hypothesis that the mode of Ca 2ϩ entry through a given VDCC subtype, rather than the total amount of Ca 2ϩ entry into the cell, is more relevant to trigger endocytosis. We have used bovine adrenal chromaffin cells because they express the same densities of VDCC subtypes than human chromaffin cells (26,54), namely, 20% L channels, 30% N channels, and 50% PQ channels (28). Despite that L channels contribute to only 20% of total whole cell current through VDCCs (2,24), Ca 2ϩ entering through slowinactivating L-type channels seems to be functionally coupled to endocytosis.…”

Past, Present and Future of Human Chromaffin Cells: Role in Physiology and Therapeutics

“…Consequently, chromaffin cells exhibit an adrenergic phenotype (Pérez-Alvarez et al 2008). In effect, when the different catecholamines preferentially released under different conditions were compared in sympathetic nerve and adrenal gland tissue, it was observed that insulin-evoked hypoglycemia and caffeine ingestion, in decreasing order of potency, predominantly induced the release of adrenaline from the adrenal medulla.…”

“…The voltage-dependent calcium channels expressed in human chromaffin cells are L-, N-, P/Q-type (Gandía et al 1998;Pérez-Alvarez et al 2008) and R-type channels (Pérez-Alvarez et al 2008). Two populations of cells can be sorted according to the major contribution of N-or P/Q-type channels (Pérez-Alvarez et al 2008), which allows for cell-type specific modulation.…”

“…Two populations of cells can be sorted according to the major contribution of N-or P/Q-type channels (Pérez-Alvarez et al 2008), which allows for cell-type specific modulation. Further, cells isolated from young individuals display prominent prepulse facilitation of L-type calcium channels, strongly coupled to quantal secretion, while cells from older subjects show only weak coupling between calcium channels and secretion (Elhamdani et al 2002).…”