CA2-DEPENDENT ACTIVATION OF T-TYPE CA2+ CHANNELS BY CALMODULIN-DEPENDENT PROTEIN-KINASE-II()

The T-type Ca2+ channel is unique among voltage-dependent Ca2+ channel s in its low threshold for opening and its slow kinetics of deactivati on. Here, we evaluate the importance of intracellular Ca2+ (Ca-i(2+)) in promoting low-threshold gating of T-type channels in adrenal glomer ulosa cells. We observe that 390 nM to 1.27 mu M Ca-i(2+) enhances T-t ype current by shifting the voltage dependence of channel activation t o more negative potentials. This Ca2+-induced shift is mediated by cal modulin-dependent protein kinase II (CaMKII), because it is abolished by inhibitors of CaMKII but not of protein kinase C and is subsequentl y restored by exogenous calmodulin. This Ca2+-induced reduction in gat ing threshold would render T-type Ca2+ channels uniquely suited to tra nsduce depolarizing stimuli of low amplitude into a Ca2+ signal suffic ient to support a physiological response.