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+ channels in its low threshold for opening and its slow kinetics of deactivation. Here, we evaluate the importance of intracellular Ca2+ (Ca-i(2+)) in promoting low-threshold gating of T-type channels in adrenal glomerulosa cells. We observe that 390 nM to 1.27 mu M Ca-i(2+) enhances T-type current by shifting the voltage dependence of channel activation to more negative potentials. This Ca2+-induced shift is mediated by calmodulin-dependent protein kinase II (CaMKII), because it is abolished by inhibitors of CaMKII but not of protein kinase C and is subsequently restored by exogenous calmodulin. This Ca2+-induced reduction in gating threshold would render T-type Ca2+ channels uniquely suited to transduce depolarizing stimuli of low amplitude into a Ca2+ signal sufficient to support a physiological response.