Activation of facilitation calcium channels in chromaffin cells by D₁ dopamine receptors through a cAMP/protein kinase A-dependent mechanism

Abstract

FACILITATION calcium channels^1–4 in unstimulated bovine chromaffin cells are normally quiescent³ but are activated by large pre-depolarizations or by repetitive depolarization in the physiological range. The activation of these 27-pS dihydropyridine-sensitive channels by repetitive stimulation^4,5, such as by increased splanchnic nerve activity, can lead to an almost twofold increase in Ca²⁺ current in these cells³. This increase in Ca²⁺ current is of probable physiological importance in stimulating rapid catecholamine secretion in response to danger or stress. We have identified D¹ dopaminergic receptors on bovine chromaffin cells by fluorescence microscopy⁶. Here we show that stimulation of the D¹ receptors activates the facilitation Ca²⁺ currents in the absence of pre-depolarizations or repetitive activity, and that activation by D₁ agonists is mediated by cyclic AMP and protein kinase A. The recruitment of facilitation Ca²⁺ channels by dopamine may form the basis of a positive feedback loop mechanism for catecholamine secretion.