EXCITATION-TRANSCRIPTION COUPLING MEDIATED BY ZINC INFLUX THROUGH VOLTAGE-DEPENDENT CALCIUM CHANNELS

Electrical activity initiates a program of selective gene expression i n excitable cells, Although such transcriptional activation is commonl y attributed to depolarization-induced changes in intracellular Ca2+, zinc represents a viable alternative given its prominent role as a cof actor in DNA-binding proteins coupled with evidence that Zn2+ can ente r excitable cells in a voltage-dependent manner. Here it is shown that Zn2+ entry into heart cells depends upon electrical stimulation and o ccurs via dihydropyridine-sensitive Ca2+ channels. The addition of ext racellular Zn2+ to spontaneously depolarizing GH3 pituitary tumor cell s induced the expression of a reporter gene driven by the metallothion ein promoter, an effect that was prevented by exposure to dihydropyrid ine Ca2+ channel blockers. Thus, Zn2+ influx through L-type Ca2+ chann els can mediate voltage-dependent gene expression.