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.
Niggli
E
E
Department of Physiology, University of Berne, Switzerland.
Rüdisüli
A
A
Maurer
P
P
Weingart
R
R
D020003:1-Octanol; D000200:Action Potentials / Q000187:drug effects; D000438:Alcohols / Q000494:pharmacology*; D000777:Anesthetics / Q000494:pharmacology*; D000818:Animals; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology; D002462:Cell Membrane / Q000502:physiology*; D004553:Electric Conductivity; D006168:Guinea Pigs; D006221:Halothane / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D006352:Heart Ventricles / Q000187:drug effects; D019850:Heptanol; D066298:In Vitro Techniques; D007700:Kinetics; D000442:Octanols / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology; D012508:Sarcolemma / Q000187:drug effects / Q000502:physiology; D012518:Sarcomeres / Q000187:drug effects / Q000502:physiology; D016276:Ventricular Function
D000438:Alcohols; D000777:Anesthetics; D015220:Calcium Channels; D000442:Octanols; D015221:Potassium Channels; D019850:Heptanol; D020003:1-Octanol; D006221:Halothane