title: Stretch-activated anion currents of rabbit cardiac myocytes.
abstract: 1. Stretch-activated anion currents were studied in sino-atrial and atrial cells using the whole-cell patch clamp technique. With continuous application of positive pressure (5-15 cmH2O) through the patch clamp electrode, the cell was inflated and the membrane conductance was increased. 2. Voltage clamp steps revealed that the stretch-activated currents had time-independent characteristics. The increase in membrane conductance was reversible on subsequent application of negative pressure to the electrode. 3. The reversal potential of the stretch-activated currents was shifted by 60 mV for a 10-fold change in intracellular Cl- concentration, while it was unaffected by replacement of Na+ in the extracellular solution by N-methyl-D-glucamine. Cell superfusion with Cl(-)-deficient solution (10 mM Cl-) reduced the amplitude of outward current. These findings indicate that the stretch-activated conductance is Cl- selective. 4. The sequence of anion permeability through the stretch-activated conductance was determined to be I-(1.7) > NO3-(1.5) > Br-(1.2) > Cl-(1.0) > and F-(0.6). SCN- appeared to be more permeant than I-. 5. The stretch-activated conductance was reduced by the Cl- channel blockers, 4,4'-dinitrostilbene-2,2'-disulphonic acid disodium salt, 4-acetamido-4'-isothiocyanatostilbene-2,2'-disulphonic acid or anthracene-9-carboxylate (9-AC). Administration of furosemide or bumetanide had no effect. 6. The stretch-activated Cl- current was recorded even though intracellular Ca2+ ions were chelated by including 10 mM EGTA in the pipette solution. Neither the specific peptide inhibitor of cyclic AMP-dependent protein kinase (50 microM), nor the non-selective blocker of protein kinases, H-7 (20 microM), was effective in reducing the stretch-activated Cl- current, suggesting that the stretch-activated Cl- current is a novel type of cardiac Cl- current, which shows a different modulatory mechanism from that of other cardiac Cl- currents.
authors.affiliation: Heart Institute of Japan, Tokyo Women's Medical College.
authors.forename: N
authors.initials: N
authors.lastname: Hagiwara
authors.forename: H
authors.initials: H
authors.lastname: Masuda
authors.forename: M
authors.initials: M
authors.lastname: Shoda
authors.forename: H
authors.initials: H
authors.lastname: Irisawa
mesh_terms: D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid / Q000494:pharmacology; D000818:Animals; D002712:Chlorides / Q000493:pharmacokinetics; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism*; D008564:Membrane Potentials; D009200:Myocardial Contraction / Q000502:physiology*; D009206:Myocardium / Q000378:metabolism*; D015221:Potassium Channels / Q000502:physiology; D011817:Rabbits; D012849:Sinoatrial Node / Q000378:metabolism; D012964:Sodium / Q000493:pharmacokinetics; D013267:Stilbenes / Q000494:pharmacology; D013997:Time Factors
chemical_list: D002712:Chlorides; D007473:Ion Channels; D015221:Potassium Channels; D013267:Stilbenes; D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid; C022306:4,4'-dinitro-2,2'-stilbenedisulfonic acid; D012964:Sodium