Elevated K(+) induces myristoylated alanine-rich C-kinase substrate phosphorylation and phospholipase D activation in glomerulosa cells.

Elevated extracellular potassium concentrations (K(+)) are known to stimulate aldosterone secretion from adrenal glomerulosa cells in vivo and in vitro. The mechanism is thought to involve depolarization-elicited activation of voltage-dependent calcium channels and an increase in calcium influx. Until now protein kinase C (PKC) was thought not to play a role in the steroidogenic response to elevated K(+). In this report, we provide evidence in bovine adrenal glomerulosa cells to suggest that elevated K(+) increases PKC activity, as shown by an enhancement in the phosphorylation of myristoylated alanine-rich C-kinase substrate (MARCKS). Elevated K(+)-induced MARCKS phosphorylation was delayed and transient and was not the result of a local production of angiotensin II (AngII). MARCKS phosphorylation in response to elevated K(+) was not accompanied by phosphoinositide hydrolysis but was inhibited by a selective PKC inhibitor. Elevated K(+) also activated phospholipase D (PLD) in a delayed but sustained manner. We propose that the observed PLD activation mediates the elevated K(+)-induced MARCKS phosphorylation via PKC, although other factors may modulate this phosphorylation event.