Swelling-activated chloride currents (ICl.swell) play an important role in cardiac electrophysiology and arrhythmogenesis. However, the regulation of these currents has not been clarified to date. In this research, we focused on the function of phenylephrine, an α1-adrenoceptor agonist, in the regulation of ICl.swell in human atrial myocytes. We recorded ICl.swell evoked by a hypotonic bath solution with the whole-cell patch-clamp technique. We found that ICl.swell increased over time, and it was difficult to achieve absolute steady state. Phenylephrine potentiated ICl.swell from −1.00 ± 0.51 pA/pF at −90 mV and 2.58 ± 1.17 pA/pF at +40 mV to −1.46 ± 0.70 and 3.84 ± 1.67 pA/pF, respectively (P < 0.05, n = 6), and the upward trend in ICl.swell was slowed after washout. This effect was concentration-dependent, and the α1-adrenoceptor antagonist prazosin shifted the dose–effect curve rightward. Addition of prazosin or the protein kinase C (PKC) inhibitor bisindolylmaleimide (BIM) attenuated the effect of phenylephrine. The PKC activator phorbol 12,13-dibutyrate (PDBu) activated ICl.swell from −1.69 ± 1.67 pA/pF at −90 mV and 5.58 ± 6.36 pA/pF at +40 mV to −2.41 ± 1.95 pA/pF and 7.05 ± 6.99 pA/pF, respectively (P < 0.01 at −90 mV and P < 0.05 at +40 mV; n = 6). In conclusion, the α1-adrenoceptor agonist phenylephrine augmented ICl.swell, a result that differs from previous reports in other animal species. The effect was attenuated by BIM and mimicked by PDBu, which indicates that phenylephrine might modulate ICl,swell in a PKC-dependent manner.
The Journal of Membrane Biology – Springer Journals
Published: Aug 26, 2014
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