title: Metabolic stress in isolated mouse ventricular myocytes leads to remodeling of t tubules.
abstract: Cardiac ventricular myocytes possess an extensive t-tubular system that facilitates the propagation of membrane potential across the cell body. It is well established that ionic currents at the restricted t-tubular space may lead to significant changes in ion concentrations, which, in turn, may affect t-tubular membrane potential. In this study, we used the whole cell patch-clamp technique to study accumulation and depletion of t-tubular potassium by measuring inward rectifier potassium tail currents (I(K1,tail)), and inward rectifier potassium current (I(K1)) "inactivation". At room temperatures and in the absence of Mg(2+) ions in pipette solution, the amplitude of I(K1,tail) measured ~10 min after the establishment of whole cell configuration was reduced by ~18%, but declined nearly twofold in the presence of 1 mM cyanide. At ~35°C I(K1,tail) was essentially preserved in intact cells, but its amplitude declined by ~85% within 5 min of cell dialysis, even in the absence of cyanide. Intracellular Mg(2+) ions played protective role at all temperatures. Decline of I(K1,tail) was accompanied by characteristic changes in its kinetics, as well as by changes in the kinetics of I(K1) inactivation, a marker of depletion of t-tubular K(+). The data point to remodeling of t tubules as the primary reason for the observed effects. Consistent with this, detubulation of myocytes using formamide-induced osmotic stress significantly reduced I(K1,tail), as well as the inactivation of inward I(K1). Overall, the data provide strong evidence that changes in t tubule volume/structure may occur on a short time scale in response to various types of stress.
authors: Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI 48109-5622, USA. lewisclf@gmail.com
authors: Lu-Feng
authors: LF
authors: Cheng
authors: Fuzhen
authors: F
authors: Wang
authors: Anatoli N
authors: AN
authors: Lopatin
mesh_terms: D000818:Animals; D003486:Cyanides / Q000494:pharmacology; D004734:Energy Metabolism / Q000187:drug effects; D005260:Female; D005559:Formamides / Q000494:pharmacology; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D017136:Ion Transport; D007700:Kinetics; D008274:Magnesium / Q000378:metabolism; D008297:Male; D008564:Membrane Potentials; D051379:Mice; D008810:Mice, Inbred C57BL; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D009997:Osmotic Pressure; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism*; D024661:Potassium Channels, Inwardly Rectifying / Q000378:metabolism*; D013312:Stress, Physiological / Q000187:drug effects; D013696:Temperature; D020257:Ventricular Remodeling / Q000187:drug effects
chemical_list: D003486:Cyanides; D005559:Formamides; D024661:Potassium Channels, Inwardly Rectifying; C031066:formamide; D008274:Magnesium; D011188:Potassium