Adrenergic-cholinergic Interactions in Left Atria: a Study Using K+ Channel Agonists, Antagonist and Pertussis Toxin

1. The role of activation of potassium conductance in the antagonism by the muscarinic agonist carbachol of positive inotropic responses to alpha- and beta-adrenoceptor stimulation was studied in electrically driven left atrial strips of the rabbit. 2. The potassium channel antagonist, 4-aminopyridine, attenuated the direct negative inotropic response to carbachol and the reversal by carbachol of positive inotropic responses to the alpha-adrenoceptor agonist phenylephrine (in the presence of timolol). The inhibitory effect of carbachol on positive inotropic responses to the beta-adrenoceptor agonist isoprenaline was much less affected by 4-aminopyridine. 3. Pretreatment of rabbits with pertussis toxin also attenuated the direct negative inotropic response to carbachol and the inhibitory effect of carbachol on positive inotropic responses to phenylephrine. 4. Neither carbachol nor phenylephrine, alone or in combination, had any effect on left atrial adenosine 3':5'-cyclic monophosphate (cyclic AMP) levels. 5. The potassium channel agonist, pinacidil, exerted a dose-dependent negative inotropic response in rabbit left atria and reversed positive inotropic responses to phenylephrine and isoprenaline. In the dose-range tested, pinacidil had a greater inhibitory effect on positive inotropic responses to phenylephrine than on positive inotropic responses to isoprenaline. 6. Pretreatment of left atria with pinacidil or cromakalim, another potassium channel agonist, antagonized positive inotropic responses to phenylephrine but not to isoprenaline. 7. These results suggest that activation of potassium conductance plays an important role in the inhibition by carbachol of positive inotropic responses of rabbit left atria to phenylephrine but not to isoprenaline.