Pertussis toxin treatment does not inhibit the effects of the potassium channel opener BRL 34915 on rat isolated vascular and cardiac tissues

Summary The experiments were undertaken to determine whether the effects of the K⁺ channel opener BRL 34915 on rat isolated vascular smooth muscle and atria were sensitive to pertussis toxin (PTx). PTx treatment of rats (100 g/kg, infused over 15 min) affected some baseline parameters of the isolated tissues: in the atria, heart rate was increased, contractile force was decreased and the basal efflux of ⁸⁶Rb⁺ was increased; in portal veins, the spontaneous activity was decreased but the contractility of aortic rings was unaffected. In the isolated atria removed from saline-treated rats, carbamylcholine decreased heart rate and contractile force, shortened the action potential duration by increasing the maximum rate of repolarization and increased ⁸⁶Rb⁺ efflux. These effects of carbamylcholine were completely abolished in the atria from PTx-treated rats, demonstrating the efficacy of the toxin. The ability of 300 M BRL 34915 and of 55 mM KCl to increase atrial ⁸⁶Rb⁺ permeability was, however, only slightly affected by PTx treatment. In portal veins from PTx-treated rats, the efficacy of BRL 34915 to inhibit spontaneous activity and to increase ⁸⁶Rb⁺ efflux was the same as in control organs. Similarly, in aortic rings, the ability of BRL 34915 to inhibit contractions to low concentrations of KCl or to noradrenaline was unaffected by PTx treatment as was the ⁸⁶Rb⁺ efflux response to BRL 34915 in this tissue. It is concluded that PTx treatment does not inhibit the effects of BRL 34915 in the tissues investigated. The results are compatible with the notion that BRL 34915 does not open K⁺ channels by acting through a PTx-sensititive G-protein. Send offprint requests to U. Quast