© 1997 American Heart Association, Inc.
Articles |
Evidence That Outwardly Rectifying Cl- Channels Underlie Volume-Regulated Cl- Currents in Heart
the Department of Pharmacology and Therapeutics (D.D., S.N.), McGill University, Montreal, Canada; the Department of Medicine (D.D., S.N.), University of Montreal; the Department of Medicine and Research Centre (D.D., S.N.), Montreal Heart Institute; and the Department of Physiology and Cell Biology (D.D., J.R.H.), University of Nevada, School of Medicine, Reno.
Correspondence to Stanley Nattel, MD, Montreal Heart Institute, 5000 Belanger St, Montreal, Quebec H1T 1C8, Canada.
Swelling-induced Cl- current (ICl.swell) is present in most cardiac tissues, but the unitary channel underlying ICl.swell is unknown. We used the cell-attached patch-clamp technique to assess the properties of single channels underlying ICl.swell and the basally active Cl- current (ICl.b) in rabbit atrial myocytes. Under isotonic conditions, single outwardly rectifying Cl- channels (ORCCs) with a slope conductance of 28±1 pS at the reversal potential were observed in 21 (5.7%) of 367 patches. Unconditional kinetic analysis revealed at least three open and four closed-channel states. Hypotonic superfusion-induced swelling resulted in the appearance of active channels in 41 (15.5%) of 265 patches without channel activity under isotonic conditions and caused a second active channel to appear in 3 of 14 patches showing a single channel under isotonic conditions. Overall, channels were seen in 54 of 336 patches under hypotonic conditions (16.1%, P<.001 versus isotonic conditions). The current-voltage relations, reversal potential–[Cl-]o relations, open probability, and kinetics of swelling-induced channels were indistinguishable from those of ORCCs under isotonic conditions. Unitary ORCCs, ICl.b, and ICl.swell were strongly and similarly inhibited by tamoxifen. Swelling-induced increases in macroscopic Cl- current were attributable to an increase in the number of active ORCCs with no significant effects on single-channel amplitude or open probability. Estimated macroscopic currents based on cell surface area, patch dimensions, single-channel ORCC current amplitude, open probability, and density were consistent with measured values of ICl.b and ICl.swell. We conclude that ORCCs underlie volume-regulated basal and swelling-induced Cl- currents in isolated rabbit atrial myocytes.
Key Words: heart • cell swelling • cardiac electrophysiology • Cl- channel • action potential
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