Hormonal regulation of calcium current in freshly isolated airway smooth muscle cells

Abstract

Single freshly isolated smooth muscle cells of adult bovine trachea were voltage clamped, and the calcium inward current was separated from K+ currents by blocking the large outward currents with intra- and extracellular Cs+ and extracellular tetraethylammonium chloride. Isoproterenol stimulated peak calcium current (ICa) in a dose-dependent manner through the beta-adrenergic receptor. The isoproterenol effect was not mediated or caused by the stimulation of a K+ or Na+ current, a decrease in the intracellular concentrations of Ca2+ or H+, the stimulation of the Na(+)-H+ or the Na(+)-Ca2+ exchanger. Neither basal nor isoproterenol-stimulated ICa was affected by internal dialysis of the cell with adenosine 3',5'-cyclic monophosphate (cAMP), cAMP analogues, or the catalytic subunit of cAMP-kinase. Internal dialysis of the cells with guanosine 5'-O-(2-thiodiphosphate) (GDP beta S) blocked the stimulation of isoproterenol whereas dialysis with guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S) induced an isoproterenol-like maximal increase of ICa. These results show that the beta-adrenergic receptor stimulates the L-type calcium current of isolated tracheal smooth muscle cells independent of cAMP and cAMP-kinase through a GTP/GDP regulated protein.

A potential site of functional modulation by protein kinase A in the cardiac Ca2+ channel α1C subunit

“…It is unclear why the smooth muscle L-type Ca 2+ currents are not enhanced by PKA [35][36][37][38]. It may be hypothesized, by analogy with oocytes and CHO cells, that in smooth muscle cells the channel is fully phosphorylated; another possibility is that a majority of the channels contain a truncated cqc subunit that, due a posttranslational modification, loses a part of its C-terminus including the residue analogous to S1928.…”

Effects of noradrenaline on membrane currents and action potential shape in smooth muscle cells from guinea‐pig ureter.

“…1) (Loirand et at. 1990;Ohya & Sperelakis, 1991;Oike et al 1992;Welling, Felbel, Peper & Hofmann, 1992). In dispersed muscle cells of the guinea-pig vas deferens and ileum (Beech, 1993) (Fish, Sperti, Colucci & Clapham, 1988;Loirand et al 1990;Oike et al 1992;Obara & Yabu, 1993 (Imaizumi et al 1989).…”

Molecular Basis for CA2+ Channel Diversity

“…The L-type calcium current of isolated tracheal smooth muscle cells is also stimulated by activation of the ß-adrenergic receptor (Welling et al 1992b). This ß-adrenergic receptor effect is mediated directly by a G-protein and not by cAMP-kinase activation.…”