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Titolo:
PERSISTENT ACTIVATION OF A SWELLING-ACTIVATED CATION CURRENT IN VENTRICULAR MYOCYTES FROM DOGS WITH TACHYCARDIA-INDUCED CONGESTIVE-HEART-FAILURE
Autore:
CLEMO HF; STAMBLER BS; BAUMGARTEN CM;
Indirizzi:
VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,DEPT PHYSIOL,POB 980551 RICHMOND VA 23298 VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,DEPT INTERNAL MED RICHMOND VA 23298 VET AFFAIRS MED CTR,DIV CARDIOL W ROXBURY MA 00000 HARVARD UNIV BOSTON MA 02115
Titolo Testata:
Circulation research
fascicolo: 2, volume: 83, anno: 1998,
pagine: 147 - 157
SICI:
0009-7330(1998)83:2<147:PAOASC>2.0.ZU;2-I
Fonte:
ISI
Lingua:
ENG
Soggetto:
MECHANOSENSITIVE ION CHANNELS; ATRIAL-NATRIURETIC-FACTOR; RABBIT CARDIAC MYOCYTES; CULTURED CHICK HEART; CELL-VOLUME; DILATED CARDIOMYOPATHY; MECHANICAL STRETCH; GENE-EXPRESSION; CONDUCTANCE; HYPERTROPHY;
Keywords:
ARRHYTHMIA; CARDIOMYOPATHY; CARDIAC EDEMA; CELL SIZE; ION CHANNEL GATING;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
79
Recensione:
Indirizzi per estratti:
Citazione:
H.F. Clemo et al., "PERSISTENT ACTIVATION OF A SWELLING-ACTIVATED CATION CURRENT IN VENTRICULAR MYOCYTES FROM DOGS WITH TACHYCARDIA-INDUCED CONGESTIVE-HEART-FAILURE", Circulation research, 83(2), 1998, pp. 147-157

Abstract

The hypothesis that cellular hypertrophy in congestive heart failure (CHF) modulates mechanosensitive (ie, swelling- or stretch-activated) channels was tested. Digital video microscopy and amphotericin-perforated-patch voltage clamp were used to measure cell volume and ion currents in ventricular myocytes isolated from normal dogs and dogs with rapid ventricular pacing-induced CHF. in normal myocytes, osmotic swelling in 0.9x to 0.6x isosmotic solution (296 mOsm/L) was required to elicit an inwardly rectifying swelling-activated cation current (I-Cir,I-swell) that reversed near -60 mV and was inhibited by 10 mu mol/L Gd3, a mechanosensitive channel blocker. Block of I-Cir,I-swell by Gd3+ simultaneously reduced the volume of normal cells in hyposmotic solutions by up to approximate to 10%, but Gd3+ bad no effect on volume in isosmotic solution. In contrast, I-Cir,I-swell was persistently activated under isosmotic conditions in CHF myocytes, and Gd3+ decreased cellvolume by approximate to 8% Osmotic shrinkage in 1.1x to 1.5x isosmotic solution inhibited both I-Cir,I-swell and Gd3+-induced cell shrinkage in CHF cells, whereas osmotic swelling only slightly increased I-Cir,I-swell, The K-0.5 and Hill coefficient for Gd3+ block of I-Cir,I-swell and Gd3+-induced cell shrinkage were estimated as approximate to 2.0 mu mol/L and approximate to 1.9, respectively, for both normal and CHF cells. In both groups, the effects of Gd3+ on current and volume were blocked by replacing bath Na+ and K+ and were linearly related with varying Gd3+ concentration and the degree of cell swelling. CHF thusaltered the set point for and caused persistent activation of I-Cir,I-swell. This current may contribute to dysrhythmias, hypertrophy, and altered contractile function in CHF and may be a novel target for therapy.

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Documento generato il 19/09/20 alle ore 09:08:48