Calcium entry mechanisms

11 June 2004

Michael Berridge

Like Ken Byron, Trevor has raised an important question concerning the operation of other entery signals. The hypothesis I proposed certainly does not preclude other entry mechanisms especially with regard to their integration into the larger issue of how they contribute to the generation of Ca²⁺ spikes. The key point is that any entry mechanism must operate in a dose dependent manner over the physiological range that induced normal Ca²⁺ spiking. In my hypothesis, I tried to explain how the conformational coupling mechanism functions to feed Ca²⁺ into the ER to sensitize the uncoupled IP₃Rs for a subsequent Ca²⁺ spike. This hypothesis certainly does not preclude other mechanisms as long as they can operate at these low agonist concentrations where entry plays a priming role. This is a somewhat different role for Ca²⁺ entry than Trevor has proposed recently where he placed most emphasis on entry contributing directly to the spike.