Automaticity of ventricular fibers induced by low concentrations of barium.
The effects of low concentrations of Ba have been studied on dog Purkinje fibers and on guinea pig left ventricular epicardium. In both tissues, Ba induces diastolic depolarization at a membrane potential more negative than -80 mV. This effect becomes clearly detectable at concentrations as low as 10-20 microM in Purkinje fibers bathed in 5.4 mM K Tyrode solution and around 100 microM in ventricular epicardium. In both tissues the Ba-induced depolarization is blocked in a dose-dependent manner by low concentrations of Cs (0.5-5 mM) as is the normal pacemaker current (if) in Purkinje fibers. In ventricular muscle the Ba-induced depolarization develops at the same rate whether the tissue is at rest or depolarized by repetitive stimulation. The maximum (initial) slope of diastolic depolarization is insensitive to D 600, La, and 4-aminopyridine, increased by tetraethylammonium chloride, decreased by tetrodotoxin, and almost entirely suppressed by Na removal. Experimental data and reconstruction of electrical activity suggest that in ventricular muscle the Ba-induced diastolic depolarization results to a large extent from the unmasking of a small pacemaker inward current, mainly carried by Na ions and similar to the pacemaker current of Purkinje fibers. Unmasking of the depolarizing effect of the pacemaker current is very likely due to the decrease by Ba of the inward going rectification. Steady-state inward Na current flowing through the Na window can increase the diastolic depolarization. Residual Cs-insensitive, Ba-induced diastolic depolarization may result from a time-dependent blockade of the background K conductance like the one described in skeletal muscle.
D015761:4-Aminopyridine; D000200:Action Potentials / Q000187:drug effects; D000631:Aminopyridines / Q000494:pharmacology; D000818:Animals; D001464:Barium / Q000494:pharmacology*; D002586:Cesium / Q000494:pharmacology; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005711:Gallopamil / Q000494:pharmacology; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D006352:Heart Ventricles; D066298:In Vitro Techniques; D007811:Lanthanum / Q000494:pharmacology; D008345:Manganese / Q000494:pharmacology; D009994:Osmolar Concentration; D010539:Permeability; D011433:Propranolol / Q000494:pharmacology; D011690:Purkinje Fibers / Q000187:drug effects; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology
D000631:Aminopyridines; D013757:Tetraethylammonium Compounds; D002586:Cesium; D001464:Barium; D005711:Gallopamil; D008345:Manganese; D019789:Tetraethylammonium; D007811:Lanthanum; D011433:Propranolol; D015761:4-Aminopyridine