Modulation of voltage-dependent facilitation of the T-type calcium current by sodium ion in isolated frog atrial cells.
Sodium ions have been reported to alter the permeation properties of L- and N-type Ca2+ channels. Here in frog atrial cardiomyocytes under whole-cell patch-clamp conditions, we have examined the effects of lowering the external Na+ concentration on the amplitude of T-type Ca2+ current, ICaT, and on the relief of its steady-state inactivation by large depolarizing prepulses, ICaT facilitation. A partial reduction in Na+ ion concentration did not significantly alter ICaT amplitude elicited at -50 mV. However, after a large depolarization, low- Na+ solutions enhanced the relief of inactivation and induced ICaT facilitation. This facilitation occurred independently of the divalent charge carrier, high intracellular Ca2+ buffering or the intracellular Na+ content. Its effects were additional to the beta-adrenergic effects mediated by a decrease of Gi/o-protein inhibitory tone. In Ca2+-free solution the very large T-type current, then carried by Na+ ions, showed only a weak relief of inactivation. In conclusion, ICaT facilitation--which, as previously reported, is modulated by the transient voltage-dependent relief of Gi-protein inhibitory tone--is further enhanced in a low-Na+ solution. In Ca2+-free solution, relief of inactivation due to re-openings dependent on the divalent charge carrier is improbable. It thus appears that for a short while after a large depolarization, external Na+ compete with Ca2+ ions on permeation-controlling sites, so as to modulate channel re-openings and thus the amplitude of voltage-facilitated ICaT independently of the control exerted by the inhibitory G-protein.
Alvarez
J L
JL
Laboratorio de Electrofisiología, Instituto de Cardiología y Cirugía Cardiovascular, La Habana, Cuba.
Artiles
A
A
Talavera
K
K
Vassort
G
G
D000818:Animals; D016275:Atrial Function; D001464:Barium / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D020747:Calcium Channels, T-Type / Q000187:drug effects* / Q000502:physiology*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D004553:Electric Conductivity; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000502:physiology; D006325:Heart Atria / Q000187:drug effects; D007700:Kinetics; D008564:Membrane Potentials; D010766:Phosphorylation; D011892:Rana catesbeiana; D011943:Receptors, Adrenergic, beta / Q000502:physiology; D012964:Sodium / Q000494:pharmacology*; D013324:Strontium / Q000378:metabolism
D020747:Calcium Channels, T-Type; D011943:Receptors, Adrenergic, beta; D001464:Barium; D004533:Egtazic Acid; D012964:Sodium; D017868:Cyclic AMP-Dependent Protein Kinases; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D002118:Calcium; D013324:Strontium