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 alpha-adrenergic agonists on the swelling-induced chloride current (ICl,swell) in canine atrial cells. ICl,swell was activated by positive-pressure inflation. 4beta-Phorbol 12, 13-dibutyrate (PDBu) concentration-dependently stimulated ICl,swell. PDBu (500 nM) increased the current density of ICl,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. 4alpha-Phorbol 12, 13-dibutyrate (4alpha-PDBu, 500 nM), an inactive analogue of PDBu, did not affect ICl,swell. The effect of PDBu was inhibited by bisindolylmaleimide I. After down regulation of PKC by phorbol 12-myristate 13-acetate (PMA, 1.6 microM, 24 h), ICl,swell no longer responded to PDBu (n=4). Neither the basal whole-cell current (prior to cell inflation) nor inflation-induced ICl,swell were affected by PKC down regulation. Phenylephrine did not affect ICl,swell. We conclude that PKC activity stimulates and does not prevent the activation of dog atrial ICl,swell. These results contrast with reports of PKC-dependent inhibition of rabbit atrial ICl,swell and currents conducted by ClC-3, a putative clone for ICl,swell. The data suggest species-dependent variations in the modulation of cardiac ICl,swell by PKC.