Increased availability and open probability of single L-type calcium channels from failing compared with nonfailing human ventricle. 1998

F Schröder, and R Handrock, and D J Beuckelmann, and S Hirt, and R Hullin, and L Priebe, and R H Schwinger, and J Weil, and S Herzig
Department of Pharmacology, University of Cologne, Germany.

BACKGROUND The role of the L-type calcium channel in human heart failure is unclear, on the basis of previous whole-cell recordings. RESULTS We investigated the properties of L-type calcium channels in left ventricular myocytes isolated from nonfailing donor hearts (n= 16 cells) or failing hearts of transplant recipients with dilated (n=9) or ischemic (n=7) cardiomyopathy. The single-channel recording technique was used (70 mmol/L Ba2+). Peak average currents were significantly enhanced in heart failure (38.2+/-9.3 fA) versus nonfailing control hearts (13.2+/-4.5 fA, P=0.02) because of an elevation of channel availability (55.9+/-6.7% versus 26.4+/-5.3%, P=0.001) and open probability within active sweeps (7.36+/-1.51% versus 3.18+/-1.33%, P=0.04). These differences closely resembled the effects of a cAMP-dependent stimulation with 8-Br-cAMP (n= 11). Kinetic analysis of the slow gating shows that channels from failing hearts remain available for a longer time, suggesting a defect in the dephosphorylation. Indeed, the phosphatase inhibitor okadaic acid was unable to stimulate channel activity in myocytes from failing hearts (n=5). Expression of calcium channel subunits was measured by Northern blot analysis. Expression of alpha1c- and beta-subunits was unaltered. Whole-cell current measurements did not reveal an increase of current density in heart failure. CONCLUSIONS Individual L-type calcium channels are fundamentally affected in severe human heart failure. This is probably important for the impairment of cardiac excitation-contraction coupling.

UI MeSH Term Description Entries
D007700 Kinetics The rate dynamics in chemical or physical systems.
D008564 Membrane Potentials The voltage differences across a membrane. For cellular membranes they are computed by subtracting the voltage measured outside the membrane from the voltage measured inside the membrane. They result from differences of inside versus outside concentration of potassium, sodium, chloride, and other ions across cells' or ORGANELLES membranes. For excitable cells, the resting membrane potentials range between -30 and -100 millivolts. Physical, chemical, or electrical stimuli can make a membrane potential more negative (hyperpolarization), or less negative (depolarization). Resting Potentials,Transmembrane Potentials,Delta Psi,Resting Membrane Potential,Transmembrane Electrical Potential Difference,Transmembrane Potential Difference,Difference, Transmembrane Potential,Differences, Transmembrane Potential,Membrane Potential,Membrane Potential, Resting,Membrane Potentials, Resting,Potential Difference, Transmembrane,Potential Differences, Transmembrane,Potential, Membrane,Potential, Resting,Potential, Transmembrane,Potentials, Membrane,Potentials, Resting,Potentials, Transmembrane,Resting Membrane Potentials,Resting Potential,Transmembrane Potential,Transmembrane Potential Differences
D009202 Cardiomyopathies A group of diseases in which the dominant feature is the involvement of the CARDIAC MUSCLE itself. Cardiomyopathies are classified according to their predominant pathophysiological features (DILATED CARDIOMYOPATHY; HYPERTROPHIC CARDIOMYOPATHY; RESTRICTIVE CARDIOMYOPATHY) or their etiological/pathological factors (CARDIOMYOPATHY, ALCOHOLIC; ENDOCARDIAL FIBROELASTOSIS). Myocardial Disease,Myocardial Diseases,Myocardial Diseases, Primary,Myocardial Diseases, Secondary,Myocardiopathies,Primary Myocardial Disease,Cardiomyopathies, Primary,Cardiomyopathies, Secondary,Primary Myocardial Diseases,Secondary Myocardial Diseases,Cardiomyopathy,Cardiomyopathy, Primary,Cardiomyopathy, Secondary,Disease, Myocardial,Disease, Primary Myocardial,Disease, Secondary Myocardial,Diseases, Myocardial,Diseases, Primary Myocardial,Diseases, Secondary Myocardial,Myocardial Disease, Primary,Myocardial Disease, Secondary,Myocardiopathy,Primary Cardiomyopathies,Primary Cardiomyopathy,Secondary Cardiomyopathies,Secondary Cardiomyopathy,Secondary Myocardial Disease
D011336 Probability The study of chance processes or the relative frequency characterizing a chance process. Probabilities
D012016 Reference Values The range or frequency distribution of a measurement in a population (of organisms, organs or things) that has not been selected for the presence of disease or abnormality. Normal Range,Normal Values,Reference Ranges,Normal Ranges,Normal Value,Range, Normal,Range, Reference,Ranges, Normal,Ranges, Reference,Reference Range,Reference Value,Value, Normal,Value, Reference,Values, Normal,Values, Reference
D002311 Cardiomyopathy, Dilated A form of CARDIAC MUSCLE disease that is characterized by ventricular dilation, VENTRICULAR DYSFUNCTION, and HEART FAILURE. Risk factors include SMOKING; ALCOHOL DRINKING; HYPERTENSION; INFECTION; PREGNANCY; and mutations in the LMNA gene encoding LAMIN TYPE A, a NUCLEAR LAMINA protein. Cardiomyopathy, Congestive,Congestive Cardiomyopathy,Dilated Cardiomyopathy,Cardiomyopathy, Dilated, 1a,Cardiomyopathy, Dilated, Autosomal Recessive,Cardiomyopathy, Dilated, CMD1A,Cardiomyopathy, Dilated, LMNA,Cardiomyopathy, Dilated, With Conduction Defect 1,Cardiomyopathy, Dilated, with Conduction Deffect1,Cardiomyopathy, Familial Idiopathic,Cardiomyopathy, Idiopathic Dilated,Cardiomyopathies, Congestive,Cardiomyopathies, Dilated,Cardiomyopathies, Familial Idiopathic,Cardiomyopathies, Idiopathic Dilated,Congestive Cardiomyopathies,Dilated Cardiomyopathies,Dilated Cardiomyopathies, Idiopathic,Dilated Cardiomyopathy, Idiopathic,Familial Idiopathic Cardiomyopathies,Familial Idiopathic Cardiomyopathy,Idiopathic Cardiomyopathies, Familial,Idiopathic Cardiomyopathy, Familial,Idiopathic Dilated Cardiomyopathies,Idiopathic Dilated Cardiomyopathy
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D006321 Heart The hollow, muscular organ that maintains the circulation of the blood. Hearts
D006352 Heart Ventricles The lower right and left chambers of the heart. The right ventricle pumps venous BLOOD into the LUNGS and the left ventricle pumps oxygenated blood into the systemic arterial circulation. Cardiac Ventricle,Cardiac Ventricles,Heart Ventricle,Left Ventricle,Right Ventricle,Left Ventricles,Right Ventricles,Ventricle, Cardiac,Ventricle, Heart,Ventricle, Left,Ventricle, Right,Ventricles, Cardiac,Ventricles, Heart,Ventricles, Left,Ventricles, Right
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man

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