title: Zinc modulation of basal and β-adrenergically stimulated L-type Ca2+ current in rat ventricular cardiomyocytes: consequences in cardiac diseases.
abstract: 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 30 nM, 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 12.7 nM. Moreover, β-adrenergic stimulation was markedly reduced by intracellular Zn(2+) at even lower concentrations (<1 nM) 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.
authors.affiliation: Laboratorio de Electrofisiología, Instituto de Cardiología y Cirugía Cardiovascular, 17 No. 702, Vedado, Havana, Cuba.
authors.forename: J
authors.initials: J
authors.lastname: Alvarez-Collazo
authors.forename: C M
authors.initials: CM
authors.lastname: Díaz-García
authors.forename: A I
authors.initials: AI
authors.lastname: López-Medina
authors.forename: G
authors.initials: G
authors.lastname: Vassort
authors.forename: J L
authors.initials: JL
authors.lastname: Alvarez
mesh_terms: D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000502:physiology*; D006331:Heart Diseases / Q000378:metabolism; D006352:Heart Ventricles / Q000166:cytology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D032383:Myocytes, Cardiac / Q000502:physiology*; D051381:Rats; D015032:Zinc / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D000318:Adrenergic beta-Agonists; D020746:Calcium Channels, L-Type; C419385:L-type calcium channel alpha(1C); D015032:Zinc; D002118:Calcium