Swelling-induced chloride-sensitive current in canine atrial cells revealed by whole-cell patch-clamp method.
An isoproterenol-induced chloride current has been detected in ventricular myocytes from guinea pig and rabbit but has not been found in canine ventricular cells. This investigation was undertaken to determine whether canine atrial cells possessed such a current. Steady-state currents were examined with potassium currents blocked by cesium. In whole-cell patch-clamp experiments, an isoproterenol-induced chloride current could not be detected shortly after patch rupture. However, whole-cell current in the absence of isoproterenol increased over time after patch rupture. The spontaneously activating steady-state current was outwardly rectifying with a reversal potential of approximately -25 mV. The current that developed over time was sensitive to variation in extracellular chloride concentration and was partially blocked by anthracene-9-carboxylic acid. Isoproterenol could enhance the amplitude of this current once it developed. Although isosmotic pipette filling and extracellular solutions were used, cell swelling was found to be the cause of the increase in whole-cell conductance that was observed during whole-cell patch-clamp experiments. The development of the current and the associated cell swelling could be prevented with the addition of 50-75 mM mannitol to the extracellular solution. The current could be observed in perforated patch recordings with nystatin when extracellular osmolarity was low (221 mosm/kg) but not when the extracellular solution was isosmotic (293 mosm/kg). Cardiac chloride currents have the potential to depolarize the resting membrane potential and cause abnormal automaticity. Chloride currents can also decrease the refractory period through a reduction in action potential duration.(ABSTRACT TRUNCATED AT 250 WORDS)
Sorota
S
S
Department of Pharmacology, Columbia University, New York, NY 10032.
D000818:Animals; D016275:Atrial Function; D002712:Chlorides / Q000502:physiology*; D003584:Cytological Techniques; D004285:Dogs; D004594:Electrophysiology; D006325:Heart Atria / Q000166:cytology* / Q000187:drug effects; D066298:In Vitro Techniques; D007249:Inflammation; D007545:Isoproterenol / Q000494:pharmacology; D008353:Mannitol / Q000494:pharmacology; D008564:Membrane Potentials; D009205:Myocarditis / Q000503:physiopathology; D009761:Nystatin / Q000494:pharmacology; D009994:Osmolar Concentration
D002712:Chlorides; D009761:Nystatin; D008353:Mannitol; D007545:Isoproterenol