Activation of a nonselective cation channel by swelling in atrial cells

Cell swelling has been shown to increase the permeability of the plasma membrane to ions such as K⁺, Na⁺, Ca²⁺ or Cl^– in many types of cells. In cardiac cells, swelling has been reported to increase Cl^– conductance, but whether cation-selective currents are activated by swelling is not known. Low Cl^– or Cl^–-free solutions were used to study the presence of such currents. Lowering the osmolarity of the extracellular medium from 299 to 219 mOsm resulted in cell swelling and concurrent activation of a cation-selective whole-cell current. When cell-attached patches were formed on swollen cells, opening of bursting single channel currents were observed in 18% of the patches studied. Ion substitution experiments indicated that the channel discriminated poorly among monovalent cations, and was impermeable to Cl^–. The channel was permeable to Ca²⁺. In symmetrical 140 mM K⁺, the current-voltage relation was linear with a single channel conductance of 36 ± 3 pS. Depolarization increased channel open probability. Interestingly, depending on the membrane patch studied, application of negative pressure to the pipette caused either an increase or a decrease in the open probability of the channel already activated by swelling. Thus, the sensitivity to tension of the swelling-activated channel was different from those of previously reported stretch-activated channels. These findings suggest that nonselective cation channels exist in rat atrial cells and may be involved in swelling-induced changes in cell function.Dr. Kim is an Established Investigator of the American Heart Association.