A role for T-type Ca2+ channels in the synergistic control of aldosterone production by ANG II and K+

Independently, plasma K+ and ANG II stimulate aldosterone secretion from ad renal glomerulosa (AG) cells, but together they synergistically control pro duction. We studied mechanisms to mediate this synergy using bovine AG cell s studied under physiological conditions (in 1.25 mM Ca2+ at 37 degrees C). Increasing K+ from 2 to 5 mM caused a potentiation of ANG II-induced aldos terone secretion and a substantial membrane depolarization (similar to 21 m V). ANG II inhibited a K+-selective conductance in both 2 and 5 mM K+ but c aused only a slight depolarization because, under both conditions, membrane potential was close to the reversal potential of the ANG II-induced curren t. ANG II activated calcium/calmadulin-dependent protein kinase II (CaMKII) equivalently in 2 and 5 mM K+. However, CaMKII activation caused a hyperpo larizing shift in the activation of T-type Ca2+ channels, such that substan tially more current was elicited at membrane potentials established by 5 mM K+. We propose that synergy in aldosterone secretion results from K+-induc ed depolarization and ANG II-induced modulation of T-type channel activatio n, such that together they promote enhanced steady-state Ca2+ flux.