86Rubidium efflux and negative inotropy induced by P1- and muscarinic-receptor agonists in guinea-pig left atria. Effects of potassium channel blockers

  • Urquhart R
  • Rothaul A
  • Broadley K
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Abstract

Guinea-pig isolated left atria, paced at 2 Hz were incubated with86rubidium (86Rb) for 120 min. They were then washed every 2 min for 2 hr, each sample being retained for scintillation counting. Left atrial isometric tension was recorded simultaneously. A concentration-response curve for the muscarinic agonist carbachol or the P1-receptor agonists adenosine and l-N6-phenylisopropyladenosine (l-PIA) was obtained. Antagonists were present from 20 min before agonist exposure. The rate constant (k) for86Rb efflux was calculated for each 2 min sample and the mean increase for each concentration of agonist determined. In the absence of drugs there was no significant alteration in the rate constant during the 2 hr experimental period. Adenosine, L-PIA and carbachol produced concentration-related increases in rate constant for86Rb efflux. The adenosine and L-PIA concentration-response curves were virtually superimposed upon the curves for the negative inotropic responses. The86Rb efflux induced by adenosine was antagonized in an apparently parallel manner by 8-phenyltheophylline (8-PT) indicating involvement of P1-receptors. Alone, the putative potassium channel blockers, 4-aminopyridine (4-AP) and bromobenzoylmethyladamantylamine (BMA) caused, respectively, no change and a reduction in resting86Rb efflux immediately prior to the agonist exposure. 4-AP reduced the L-PIA- and adenosine-induced increases in86Rb efflux and, to a lesser extent, the negative inotroplc response to adenosine. BMA caused "flattening" of the dose-response curves for86Rb efflux induced by L-PIA, adenosine and carbachol with a significant reduction in response at the highest concentrations of adenosine and carbachol. The negative inotroplc response to adenosine was also reduced. These results suggest that 4-AP and BMA block the P1-receptor-linked potassium channels and that BMA interacts with common K+channels linked to P1- and muscarinic receptors. The negative inotroplc responses of the guinea-pig left atrium to P1- and muscarinic agonists can be attributed, at least in part, to the opening of outward K+channels. © 1991.

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Authors

  • Robert A. Urquhart

  • Alan L. Rothaul

  • Kenneth J. Broadley

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