ALPHA-1-ADRENOCEPTORS REDUCE BACKGROUND K+ CURRENT IN RABBIT VENTRICULAR MYOCYTES

1. Ventricular myocytes were isolated by enzymatic dispersion of adult rabbit hearts, and voltage clamped using the whole-cell variation of the patch clamp technique. Experiments were carried out at either 35-degrees-C or room temperature (21-23-degrees-C). 2. In the presence of 10(-3) M-4-aminopyridine to block the transient outward K+ current, and 10(-6) M-propranolol to block beta-adrenoceptors, the alpha-1-adrenergic agonist methoxamine produced action potential prolongation, and a small depolarization of the diastolic membrane potential. Under voltage clamp conditions, methoxamine decreased the magnitude of the inward rectifier K+ current, I(K1), in both the inward and outward directions. This effect was dose dependent (10(-5)-10(-3) M) and fully reversible upon wash-out of the agonist. 3. The neurotransmitter noradrenaline (10(-6) -2 x 10(-5) M), in the presence of propranolol (10(-6) M), also reduced I(K1) in ventricular cells, and this effect was blocked by the specific alpha-1-adrenoceptor antagonist prazosin. 4. The alpha-1-adrenoceptor-mediated decrease in I(K1) in ventricular myocytes was not affected by pre-incubation of the cells with 0.5-mu-g/ml pertussis toxin (8-10 h, 30-32-degrees-C). This result suggests that in rabbit ventricular cells, the alpha-1-modulation of I(K1) occurs via a pertussis toxin-insensitive guanine nucleotide-binding regulatory protein. 5. These observations demonstrate that I(K1) in ventricular myocytes can be modulated by cardiac alpha-1-adrenoceptors. The resulting changes in action potential repolarization and diastolic membrane potential may have significant effects on cardiac performance.