Activation of gadolinium-sensitive ion channels in cardiomyocytes in early adaptive stages of volume overload-induced heart failure

Academic Article

Abstract

  • Objective: The objective of this study was to investigate whether gadolinium (Gd )-sensitive stretch-activated ion channels (SAC) are basally active in left ventricular (LV) myocytes in early stages of heart failure (HF) induced by volume overload. Methods: The aortocaval fistula (ACF) model was employed to induce HF due to volume overload in rat. At specific time-points, LV myocytes were acutely isolated using a modified Langendorff apparatus. Whole-cell currents were measured using the patch-clamp technique and intracellular Ca (Ca ) was examined using fluorescence imaging and the Ca -sensitive dye Fura-2. Results: Current-voltage data were obtained from sham and ACF myocytes at 5-d and 2-, 6-, 8- and 10-wk post surgery. Compared to data from matching sham rats, a 10 μM Gd -sensitive current at - 100 mV comprised a larger fraction of total current in myocytes from 5-d, 2-wk, and 6-wk ACF rats. In general, the Gd -sensitive current contributed to inward currents at mV ≤ - 80 and outward currents at > + 20 mV. The enhanced Gd -sensitive current was absent in myocytes from 8- and 10-wk ACF rats. 10 or 100 μM Gd had no appreciable effect on resting Ca of myocytes from 5-d ACF or corresponding sham rats. The Gd -sensitive current in 5-d ACF myocytes was i) sensitive to the cation-selective SAC inhibitor, GsMTx-4, ii) non-selective for Na /K , and iii) impermeable to Ca . Conclusion: A basally-active, Gd - and GsMTx-4-sensitive SAC current that is non-selective for Na and K , but impermeable to Ca under resting conditions is transiently elevated in LV myocytes from rats in early stages of volume overload-induced HF. © 2006 European Society of Cardiology. 3+ 2+ 2+ 2+ 3+ 3+ 3+ 3+ 2+ 3+ + + 2+ 3+ + + 2+ i i
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    Author List

  • McNicholas-Bevensee CM; DeAndrade KB; Bradley WE; Dell'Italia LJ; Lucchesi PA; Bevensee MO
  • Start Page

  • 262
  • End Page

  • 270
  • Volume

  • 72
  • Issue

  • 2