Influence of divalent cations on rabbit atria and modification of catecholamine response on pacemaker cells

Spontaneously beating isolated atria of rabbits responded to Mn++ and Co++ with a progressively increasing negative chronotropism and inotropism, which was reversible by washout and by elevating the bath concentration of Ca++. The cumulative dose response curve for adrenaline for chronotropic response was markedly shifted to the right in the presence of Mn++ or Co++. This effect was also reversible. Verapamil produced only a moderate decline in spontaneous rate and contractility and did not block the chronotropic response to adrenaline. It is concluded that Mn++ and Co++ block the action of catecholamine on the pacemaker cells and they differ at least in part from organic calcium channel antagonists in their mechanism of action.