Comparative electrophysiological and mechanical actions of ATP-sensitive potassium channel openers in canine Purkinje fibers.
1. Electrophysiological and mechanical effects of ATP-dependent potassium channel openers on canine Purkinje fibers were examined. 2. Cromakalim and pinacidil (0.3-10 microM) and nicorandil (0.3-1 mM) shortened the action potential duration (APD), and reduced the contractile force, in a concentration-dependent manner. Other action potential parameters were unaffected. The effects were reversible. 3. Effects of the openers were antagonized by tetraethylammonium (a non-specific potassium channel blocker) and more potently by glibenclamide (a blocker of ATP-sensitive K+ channel). 4. The APD shortening and the negative inotropic effect induced by a switch of stimulation frequency (from 0.5 to 3 Hz) were potentiated by the openers. At high Ca2+ (5.4 and 10.8 mM), the effects of the openers on the APD and contractile force were unaffected. 5. In the spontaneously beating preparations, the openers hyperpolarized the maximum diastolic potential, and an arrest occurred. 6. Under the calcium overload condition, the K+ openers abolished a delayed after depolarization, and enhanced the depressed post-rest potentiation. 7. These results suggest that the K+ channel openers increase the K+ conductance and might decrease the cellular Ca2+ level in calcium overloading cells, and that nicorandil might also act directly ATP-sensitive K+ channels.
Satoh
H
H
Department of Pharmacology, Nara Medical University, Japan.
D000200:Action Potentials / Q000187:drug effects; D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology; D019806:Cromakalim; D004285:Dogs; D004594:Electrophysiology; D005905:Glyburide / Q000494:pharmacology; D006146:Guanidines / Q000494:pharmacology; D066298:In Vitro Techniques; D009200:Myocardial Contraction / Q000187:drug effects*; D009536:Niacinamide / Q000031:analogs & derivatives / Q000494:pharmacology; D020108:Nicorandil; D020110:Pinacidil; D015221:Potassium Channels / Q000187:drug effects*; D011690:Purkinje Fibers / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D011758:Pyrroles / Q000494:pharmacology; D013757:Tetraethylammonium Compounds / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
D001578:Benzopyrans; D006146:Guanidines; D015221:Potassium Channels; D011758:Pyrroles; D013757:Tetraethylammonium Compounds; D014665:Vasodilator Agents; D019806:Cromakalim; D009536:Niacinamide; D020108:Nicorandil; D020110:Pinacidil; D000255:Adenosine Triphosphate; D005905:Glyburide