Protein kinase C stimulates swelling-induced chloride current in canine atrial cells

The whole-cell patch-clamp technique was used to study the effect of protein kinase C (PKC) stimulation and a-adrenergic agonists on the swelling-induced chloride current (I-Cl,I-swell) in canine atrial cells. I-Cl,I-swell was activated by positive-pressure inflation. 4 beta-Phorbol 12, 13-dibutyrate (PDBu) concentration-dependently stimulated I-Cl,I-swell. PDBu (500 nM) increased the current density of I-Cl,I-swell from 9.1 +/- 1.3 to 24.2 +/- 4.8 pA/pF at +20 mV (n = 4). This effect developed slowly, reaching a steady-state after more than 5 min of exposure. 4 alpha-Phorbol 12, 13-dibutyrate (4 alpha-PDBu, 500 nM), an inactive analogue of PDBu, did not affect I-Cl,I-swell. The effect of PDBu was inhibited by bisindolylmaleimide I. After down regulation of PKC by phorbol 12-myristate 13-acetate (PMA, 1.6 mu M, 24 h), I-Cl,I-swell no longer responded to PDBu (n = 4). Neither the basal whole-cell current (prior to cell inflation) nor inflation-induced ICI,swell were affected by PKC down regulation. Phenylephrine did not affect I-Cl,I-swell. We conclude that PKC activity stimulates and does not prevent the activation of dog atrial I-Cl,I-swell. These results contrast with reports of PKC-dependent inhibition of rabbit atrial I-Cl,I-swell and currents conducted by CIC-3, a putative clone for I-Cl,I-swell. The data suggest species-dependent variations in the modulation of cardiac I-Cl,I-swell by PKC.