Evidence of a new, preferentially Mg-carrying, transport system besides the fast Na and the slow Ca channels in the excited myocardial sarcolemma membrane

Abstract

MgCl 2 added to a K-rich (19 m m Ca-deficient (0.4 m m) Tyrode solution in a suitably high concentration (14 to 34 m m Mg) maintains or restores electric excitability, overshoot and propagated action potentials. The experiments reveal the true existence of a special transport system for the Mg entry into the ventricular myocardium that can be distinguished from both the fast Na and the slow Ca channels by means of certain drugs and appropriate electrophysiological techniques. The transmembrane transport systems for Na, Mg, and Ca ions differ with respect to their sensitivities to graded membrane depolarizations. The Na channel is most easily inactivated at a reduced level of membrane potential, whereas the Ca channel is most resistant. The Mg channel has an intermediate position. Ca-mediated action potentials are selectively blocked by specific Ca-antagonists such as verapamil, D 600, nifedipine or diltiazem. However, Mg-carried action potentials are refractory to these inhibitors. Tetrodotoxin and lidocaine are capable of suppressing both the transmembrane Na and Mg influxes without affecting the slow Ca channel. β-Adrenergic catecholamines influence the myocardial Mg and Ca currents in an exactly opposite sense: β-adrenergic substances largely promote myocardial Ca uptake and Ca-dependent action potentials whereas they totally block the transmembrane Mg fluxes into the partially depolarized myocardial fibres and, thereby, inhibit every Mg-dependent biolectric activity. Hence the usual “two-channel concept” that only allowed for a fast Na and a slow Ca inward current, but ignored the existence of a third transmembrane transport system that preferentially carries Mg ions into the ventricular myocardium, has to be considered as an oversimplification. It is suggested that the reciprocal effects of β-adrenergic catecholamines on the inward fluxes of Ca and Mg ions serve to maximize the contractile responses to β-receptor stimulation. The intensification by β-adrenergic catecholamines of the Ca influx simultaneously with a restriction of the transmembrane supply of Ca-antagonistic Mg ions will activate Ca-dependent excitation-contraction coupling of the ventricular myocardium in the most effective manner.