Stretch-activated anion currents of rabbit cardiac myocytes

J Physiol. 1992 Oct;456:285-302. doi: 10.1113/jphysiol.1992.sp019337.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid / pharmacology
  • Animals
  • Chlorides / pharmacokinetics
  • In Vitro Techniques
  • Ion Channels / drug effects
  • Ion Channels / metabolism*
  • Membrane Potentials
  • Myocardial Contraction / physiology*
  • Myocardium / metabolism*
  • Potassium Channels / physiology
  • Rabbits
  • Sinoatrial Node / metabolism
  • Sodium / pharmacokinetics
  • Stilbenes / pharmacology
  • Time Factors

Substances

  • Chlorides
  • Ion Channels
  • Potassium Channels
  • Stilbenes
  • 4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid
  • 4,4'-dinitro-2,2'-stilbenedisulfonic acid
  • Sodium