The effect of oligomycin on the electrical activity of frog atrial muscle and the effect of variation of [Ca2+]0 concentration

The effect of oligomycin on electrical activity in frog atrial fibers has been studied using the current and voltage clamp double sucrose gap technique. Also, the accompanying contraction has been measured. Current clamp studies showed that oligomycin reduced both peak amplitude and duration of the action potential, and also the contractile force; the effect increasing with concentration. Recovery occurred following washout, but this also was dependent on concentration on inhibitor, with recovery not being achieved if concentration of inhibitor exceeded a given value. Voltage clamp demonstrated a marked reduction in the slow inward current amplitude and a negative shift of the reversal potentials. In addition, oligomycin induced a slight increase in the delayed outward current, this increase not occurring in the early repolarization phase of the action potential. In the presence of oligomycin with excess [Ca²⁺]₀ the action potential shortened, but its amplitude increased. Excess [Ca²⁺]₀ during inhibition also increased the slow inward current amplitude and shifted the reversal potential toward a more positive value. These results suggest that when the coupling of respiration with oxidative phosphorylation is inhibited the level of ATP in the sarcoplasm is decreased, leading to an increase in intracellular free Ca²⁺ concentration, thereby reducing the transmembrane Ca²⁺ concentration gradient. This decreases the Ca²⁺ driving force which is Ca-dependent and alters the action potential amplitude, together with the slow channel conductance (which is Ca²⁺ dependent) leading to a reduction of excitation-contraction coupling.