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

Abstract

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