Electrical and Secretory Response to Cholinergic Stimulation in Mouse and Human Adrenal Medullary Chromaffin Cells

Abstract

Chromaffin cells from the adrenal gland secrete catecholamines in response to acetylcholine (ACh).^(1,2) ACh induces a transient depolarization of the adrenal chromaffin cell membrane, which in some animals is due to the opening of nicotinic-receptor channels.^(3–7) It has been observed that the ACh-induced depolarization is often accompanied by the generation of action potentials or by a marked increase in the frequency of spontaneously occuring action potentials.^(3,6–9) These action potentials are presumably due to the activation of both Na+ and Ca²⁺ voltage-gated ionic channels. Blocking Na ⁺ -channels with tetrodotoxin (TTX) leads to a partial inhibition of the stimulated release of catecholamines.^(10,11) This result suggests that Ca²⁺ entry associated with the ACh-evoked depolarization is reduced in the presence of TTX.^(10,11) The rapid depolarization resulting from the activation of Na⁺ -channels should enhance Ca²⁺ entry by recruitment of Ca²⁺ -channels with a more positive potential for activation. This is presumably the physiological pathway for Ca²⁺ entry at low concentrations of ACh (10 μM). At high concentrations of ACh (55 μM), however, additional Ca²⁺ entry occurs through the ACh nicotinic-receptor channel.⁽¹²⁾ While Ca²⁺ entry through the ACh-channel is restricted to the small region of clustered nicotinic-receptor channels, voltage-dependent Ca²⁺ -channels are probably evenly distributed over the entire cell surface as patch-clamp⁽⁹⁾ and other studies⁽¹³⁾ appear to indicate.