Attenuation by magnesium of the electrophysiologic effects of hyperkalemia on human and canine heart cells

Because magnesium (Mg⁺⁺) has been shown to promote maintenance of a negative resting potential it might oppose the depolarizing effect of potassium (K⁺) in cardiac cells. To test this hypothesis the electrocar diographic changes that occur during hyperkalemia were prospectively studied in 11 patients, 4 of whom had hypermagnesemia. Action potential studies were carried out in single atrial and ventricular cells isolated from 11 canine hearts using similar extracellular concentrations of Mg⁺⁺ _° and K⁺ _° to elucidate further the relative effects of these cations. Hyperkalemia was associated with a marked reduction in P wave amplitude and marked prolongation of the QRS complex. However, normal P waves and normal QRS durations were recorded in hyperkalemic patients with excess Mg⁺⁺ (2.5 mEq/liter or more). Mg⁺⁺ also antagonized some effects of K⁺ in the isolated atrial and ventricular tissues. With elevated levels of [Mg⁺⁺] the K⁺-induced depolarization of the resting potential was less than half as much as when [Mg⁺⁺]was normal (9 versus 21 mV in ventricular cells and 18 versus 40 mV in atrial cells). Furthermore, the fall in linear conduction velocity that accompanied elevated [K⁺]levels in ventricular cells failed to occur when the level of [Mg⁺⁺]was high. Mg⁺⁺-K⁺ antagonism helps to explain the preservation of a normal P wave because the onset of K⁺ effects in isolated atrial cells was delayed when [Mg⁺⁺]was high and action potential amplitude was improved. It is concluded that the heart cells of patients with high serum levels of [Mg⁺⁺]were less sensitive to an increase in [K⁺]than were those of patients with lower [Mg⁺⁺]and, accordingly, that Mg⁺⁺ attenuated the electrophysiologic response to elevated [K⁺].