Metabolic inhibition enhances Ca(2+)-activated K+ current in smooth muscle cells of rabbit portal vein.
The effect of metabolic inhibition on macroscopic and single-channel K+ currents in isolated rabbit portal vein myocytes was investigated by patch-clamp technique. Depression of adenosine triphosphate synthesis was produced by 2-deoxy-D-glucose (10 mM) and either cyanide (2 mM) or dinitrophenol (50 microM). Outward quasi-steady-state current evoked by a ramp protocol and outward time-dependent current during step depolarizations were increased during metabolic inhibition. The reversal potential for quasi-steady-state current shifted negatively toward equilibrium potential of K+ during treatment consistent with a role for K+ conductance and hyperpolarization of membrane potential. The macroscopic K+ current affected was 1) voltage dependent, 2) inhibited by intracellular Ca2+ chelation and low tetraethylammonium ion (1 mM) but unaffected by 4-aminopyridine (2 mM), and 3) associated with a rise in intracellular Ca2+ assessed by indo 1. Metabolic inhibition caused an increase in voltage-dependent large-conductance K+ channel (120-130 pS) activity in cell-attached patches of myocytes bathed in physiological solution (140 mM K+ in pipette). The channels were blocked in a flickery fashion by tetraethylammonium ion (0.5 mM) and inhibited with charybdotoxin (100 nM). We conclude that metabolic inhibition increases the activity of large-conductance Ca(2+)-activated K+ channels in vascular smooth muscle.
Miller
A L
AL
Department of Physiology, St. Boniface Research Centre, University of Manitoba, Winnipeg, Canada.
Morales
E
E
Leblanc
N R
NR
Cole
W C
WC
D019297:2,4-Dinitrophenol; D000255:Adenosine Triphosphate / Q000037:antagonists & inhibitors*; D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D003486:Cyanides / Q000494:pharmacology; D003847:Deoxyglucose / Q000494:pharmacology; D004140:Dinitrophenols / Q000494:pharmacology; D004533:Egtazic Acid / Q000494:pharmacology; D004558:Electric Stimulation; D004594:Electrophysiology; D006706:Homeostasis; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D011169:Portal Vein / Q000166:cytology / Q000378:metabolism*; D011188:Potassium / Q000502:physiology*; D011817:Rabbits; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology
D003486:Cyanides; D004140:Dinitrophenols; D013757:Tetraethylammonium Compounds; D004533:Egtazic Acid; D019789:Tetraethylammonium; D000255:Adenosine Triphosphate; D003847:Deoxyglucose; D019297:2,4-Dinitrophenol; D011188:Potassium; D002118:Calcium