Phenylephrine enhanced swelling-activated chloride current in human atrial myocytes

Abstract

Objective To study the function of phenylephrine, an α1-adrenoceptor agonists, in the regulation of swelling-activated chloride current ( ICl.swell) in human atrial myocytes by a whole-cell patch-clamp technique. Methods Atrial myocytes were isolated from specimens of right atrial appendage obtained from patients undergoing coronary artery bypass and enzymatically dissociated. The myocytes were perfused with isotonic bath solution (1.0T) or hyposmotic bath solution (0. 6-times isosmotic, 0. 6 T),and exposured to phenylephrine, 4,4'-diisothiocyanostilbene-2,2' disulfonicacid (DIDS), or prazosin, an α1-adrenoceptor antagonis respectively. The currents under different conditions were compared. Results ICl.swell evoked by hyposmotic bath solution was recorded. After approaching steady state values, subsequent exposure to 100 μmol/L phenylephrine caused enhancement of ICl.swell. The current was increased from (-1.11±0.55) pA/pF to ( - 1.56 ±0.69) pA/pF at -90 mV (P<0.05,n=7) and from (3.24±2.04) pA/pF to (4.64±2.61) pA/pF at +40 mV (P<0. 01,n=7) respectively. This effect was concentration-dependent, and could be reversed by DIDS or after exposure to the isotonic solution. Application of 1 μmol/L prazosin could attenuate the effect of phenylephrine. Conclusion Phenylephrine can enhance ICl.swell in human atrial myocytes, which is distinct from the reports in other species, indicating distinguished species-dependent variations in the modulation of ICl.swell, in atrial myocytes by phenylephrine. Key words: Chloride current; Phenylephrine; α1-adrenoceptor agonist; Atrial myocyte