Effects of K+-channel blockers on A(1)-adenosine receptor-mediated negative inotropy and chronotropy of guinea-pig isolated left and right atria

Adenosine has previously been shown to stimulate K+-efflux and to block L-t ype calcium channels in atrial myocytes. The aim of the present study was t o evaluate the contribution of K+-channels in the development of the negati ve inotropic and chronotropic responses to adenosine agonists in guinea-pig left and right atria, respectively. Tetraethylammonium (TEA) potentiated t he negative inotropic and chronotropic responses to R-(-)-N-6-(2-phenyl-iso propyl)-adenosine (R-PIA), seen as leftward shifts of the concentration-res ponse curves. Glibenclamide had no effect on the negative inotropic respons e to R-PIA but increased the rate of onset of the negative chronotropic res ponse in right atria. 4-Aminopyridine (4-AP, 10 mM), potentiated the left a trial inotropic responses to R-PIA, seen as a leftward shift of the concent ration-response curve, but slowed the speed of onset of the response to a s ingle concentration (10(-6) M) of R-PIA. This reduction in speed of onset o f the response can explain the differences in effects of 4-AP on concentrat ion-response curves reported here and previously. In the right atria, 4-AP (10 mM) inhibited the negative chronotropic responses to R-PIA, seen as a. rightward shift of the concentration-response curve and reduction of the ma ximum response. 4-AP also slowed the onset of the right atrial rate respons e to R-PIA. These results support the theory that K+-efflux plays only a mi nor role in the negative inotropic responses of guinea-pig left atl ia to R -PIA. This apparently controls the speed of onset of the response. The nega tive chronotropic response of guinea-pig right atria to R-FIA appears to be much more dependent upon K+-efflux than for the negative inotropic respons e of the left atria. (C) Elsevier, Paris.