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pubmed:abstractText |
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, IK1, 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 IK1 in ventricular cells, and this effect was blocked by the specific alpha 1-adrenoceptor antagonist prazosin. 4. The alpha 1-adrenoceptor-mediated decrease in IK1 in ventricular myocytes was not affected by pre-incubation of the cells with 0.5 micrograms/ml pertussis toxin (8-10 h, 30-32 degrees C). This result suggests that in rabbit ventricular cells, the alpha 1-modulation of IK1 occurs via a pertussis toxin-insensitive guanine nucleotide-binding regulatory protein. 5. These observations demonstrate that IK1 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.
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