Modulation of spontaneous transient Ca2+-activated K+ channel currents by cADP-ribose in vascular smooth muscle cells.
Transient local releases of Ca(2+) from the sarcoplasmic reticulum activate nearby Ca(2+)-activated K(+) channels to produce spontaneous transient outward current (STOC) in smooth muscle cells. We examined if cADP-ribose, an endogenous mediator of Ca(2+) release channels of the sarcoplasmic reticulum, could modify STOC activity. In freshly isolated rat tail arterial cells, cADP-ribose (5 microM) increased STOC frequency significantly from 308+/-26.2 to 398.8+/-28.8 per minute. The average current at a test potential of -20 mV was increased significantly from 47.8+/-0.7 to 101.1+/-0.7 pA in the presence of cADP-ribose. The cell permeant antagonist 8-bromo-cADP-ribose (50 microM) reduced significantly the STOC frequency to 52.5+/-7.5 per minute and the average current to 24.7+/-0.1 pA. The STOCs were inhibited significantly by ryanodine (1 microM) and charybodotoxin (150 nM). These findings suggest the presence of basal cADP-ribose activity in resting vascular smooth muscle cells and that STOC activity is stimulated by cADP-ribose.
Cheung
Donald W
DW
University of Ottawa Heart Institute, 40 Ruskin Street, K1Y 4W9, Ottawa, Canada. dcheung@ottawaheart.ca
D000818:Animals; D018999:Charybdotoxin / Q000494:pharmacology; D036563:Cyclic ADP-Ribose / Q000031:analogs & derivatives* / Q000494:pharmacology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D024681:Potassium Channels, Calcium-Activated / Q000502:physiology*; D051381:Rats; D012433:Ryanodine / Q000494:pharmacology
C106570:7-deaza-8-bromo-cyclic ADP-ribose; D024681:Potassium Channels, Calcium-Activated; D018999:Charybdotoxin; D036563:Cyclic ADP-Ribose; D012433:Ryanodine