Zinc modulation of basal and β-adrenergically stimulated L-type Ca2+ current in rat ventricular cardiomyocytes: consequences in cardiac diseases

来自 EBSCO

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摘要：

Zinc exists in biological systems as bound and histochemically reactive free Zn 2+ in the nanomolar range. Zinc is required as either structural or catalytic component for a large number of enzymes. It also modulates current passage through many ion channels. Here, we reinvestigated the effects of extracellular and intracellular Zn 2+ on the L-type Ca 2+ current ( I CaL ) and its modulation by β-adrenergic stimulation in rat ventricular cardiomyocytes. In the absence of Ca 2+ ions, Zn 2+ could permeate through the L-type channel at much lower concentrations and at a more positive voltage range, but with a lower permeability than Ca 2+ . In the presence of Ca 2+ , extracellular Zn 2+ demonstrated strong bimodal inhibitory effects on the I CaL , with half-inhibition occurring around 30nM, i.e., in the range of concentrations found in the plasma. Intracellular Zn 2+ also significantly inhibited the I CaL with a half-inhibitory effect at 12.7nM. Moreover, β-adrenergic stimulation was markedly reduced by intracellular Zn 2+ at even lower concentrations (<1nM) as a consequence of Zn 2+ -induced inhibition of the adenylyl cyclase. All these effects appeared independent of redox variations and were not affected by dithiothreitol. Thus, both basal intracellular and extracellular Zn 2+ modulate transmembrane Ca 2+ movements and their regulation by β-adrenergic stimulation. Considering that, in many pathological situations, including diabetes, the extracellular Zn 2+ concentration is reduced and the intracellular one is increased, our results help to explain both Ca 2+ overload and marked reduction in the β-adrenergic stimulation in these diseases.

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关键词：

Divalent cations Zinc homeostasis Intracellular signaling Patch clamp Neuromediator

DOI：

10.1007/s00424-012-1162-3

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年份：

2012