Modulation of Ca2+ channel selectivity and cardiac contraction by photorelease of Ca2+

The effect of rapid increases of extracellular Ca2+ concentration on tension development and Ca2+ channel selectivity has been investigated in frog (Rana pipiens) ventricular myocardium using a novel light-sensitive Ca2+ chelator, dimethoxy-nitrophen. Dimethoxy-nitrophen is a photolabile tetracarboxylate Ca2+ chelator that on photolysis to dicarboxylate fragments alters its affinity (Kd) for Ca2+ from 5 X 10(-9) to 2 X 10(-3) M. A single 160-microseconds ultraviolet light pulse induced the release of approximately 80-100 microM Ca2+ with a half-time of 200 microseconds. In low extracellular Ca2+ concentration, Na+ current through the Ca2+ channel was blocked by photorelease of extracellular Ca2+ in less than 500 microseconds; nevertheless, 60-80 ms were required to activate or enhance tension. Enhancement of tension was more effective when Ca2+ was released during the activation of the Ca2+ channel than during its inactivation. The voltage dependence of enhanced tension, caused by photorelease of Ca2+, was bell shaped and was similar to that of Ca2+ current. These findings suggest that Ca2+ transport through the Ca2+ channel is the primary mechanism for the transport of Ca2+ to activate tension in the frog heart. The use of dimethoxy-nitrophen makes it possible to examine the rapid kinetics of the Ca-dependent processes involved in regulation of channel function and contraction.