Distinct Intracellular Calcium Profiles Following Influx Through N- Versus L-Type Calcium Channels: Role of Ca -Induced Ca Release

Tully, Keith and Steven N. Treistman. Distinct intracellular calcium profiles following influx through Nversus L-type calcium channels: role of Ca -induced Ca release. J Neurophysiol 92: 135–143, 2004; 10.1152/jn.01004.2003. Selective activation of neuronal functions by Ca is determined by the kinetic profile of the intracellular calcium ([Ca ]i) signal in addition to its amplitude. Concurrent electrophysiology and ratiometric calcium imaging were used to measure transmembrane Ca current and the resulting rise and decay of [Ca ]i in differentiated pheochromocytoma (PC12) cells. We show that equal amounts of Ca entering through N-type and L-type voltage-gated Ca channels result in significantly different [Ca ]i temporal profiles. When the contribution of N-type channels was reduced by -conotoxin MVIIA treatment, a faster [Ca ]i decay was observed. Conversely, when the contribution of L-type channels was reduced by nifedipine treatment, [Ca ]i decay was slower. Potentiating L-type current with BayK8644, or inactivating N-type channels by shifting the holding potential to 40 mV, both resulted in a more rapid decay of [Ca ]i. Channel-specific differences in [Ca 2 ]i decay rates were abolished by depleting intracellular Ca stores with thapsigargin or by blocking ryanodine receptors with ryanodine, suggesting the involvement of Ca -induced Ca release (CICR). Further support for involvement of CICR is provided by the demonstration that caffeine slowed [Ca ]i decay while ryanodine at high concentrations increased the rate of [Ca ]i decay. We conclude that Ca 2