Effects of general anesthetics on current flow across membranes in guinea pig myocytes

Myocytes were isolated from adult guinea pig ventricles. Whole cell, tight-seal recording was employed to investigate the electrical properties of the junctional (nexal membrane) and nonjunctional membrane (sarcolemma) under the influence of n-alkanols (heptanol, octanol) and halothane. Studies of cell pairs with a double voltage-clamp approach showed that these agents give rise to a reversible electrical uncoupling. Examination of single myocytes with a single voltage-clamp method showed that these substances modify several sarcolemmal current systems. The slope conductance was reduced over the entire voltage range examined (-90 to +50 mV). The Ca2+ inward current (Isi) showed a decreased amplitude and an accelerated inactivation. The repriming of Isi remained unchanged. The steady-state inactivation of Isi was shifted by 2-3 mV toward more negative potentials. Optical measurements demonstrated an increase in sarcomere spacing at rest and a decrease during peak systolic shortening. The results suggest that n-alkanols and halothane exert their effects on membrane currents via incorporation into the lipid bilayer.