Excitation-transcription coupling mediated by zinc influx through voltage-dependent calcium channels.
Electrical activity initiates a program of selective gene expression in excitable cells. Although such transcriptional activation is commonly attributed to depolarization-induced changes in intracellular Ca2+, zinc represents a viable alternative given its prominent role as a cofactor in DNA-binding proteins coupled with evidence that Zn2+ can enter excitable cells in a voltage-dependent manner. Here it is shown that Zn2+ entry into heart cells depends upon electrical stimulation and occurs via dihydropyridine-sensitive Ca2+ channels. The addition of extracellular Zn2+ to spontaneously depolarizing GH3 pituitary tumor cells induced the expression of a reporter gene driven by the metallothionein promoter, an effect that was prevented by exposure to dihydropyridine Ca2+ channel blockers. Thus, Zn2+ influx through L-type Ca2+ channels can mediate voltage-dependent gene expression.
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Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
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Appel
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Gao
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Marban
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D000818:Animals; D001692:Biological Transport; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism* / Q000502:physiology; D002478:Cells, Cultured; D004558:Electric Stimulation; D005453:Fluorescence; D006352:Heart Ventricles / Q000166:cytology / Q000378:metabolism; D015640:Ion Channel Gating; D051381:Rats; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured; D016276:Ventricular Function; D015032:Zinc / Q000378:metabolism*
D015220:Calcium Channels; D015032:Zinc; D002118:Calcium