L-type calcium currents of human myocytes from ventricle of non-failing and failing hearts and from atrium. 1994

T Mewes, and U Ravens
Institut für Pharmakologie, Universität GH Essen, Germany.

L-type calcium currents were studied in ventricular myocytes isolated from non-failing hearts, i.e. donor hearts not suitable for transplantation, and from severely failing hearts, i.e. explanted hearts of organ recipients, in order to identify possible alterations of the currents in cardiomyopathy. Human atrial myocytes were investigated for comparative purposes. As deficient production of cyclic AMP might contribute to the development of cardiac failure, the responses to forskolin, a direct stimulator of adenylyl cyclase, were also studied. The patch-clamp technique was applied in the single electrode whole-cell mode. Calcium currents were similar in myocytes from non-failing and failing hearts: Maximum current-densities were 3.8 v 3.1 pA/pF, and 2.2 pA/pF in atrial cells. In human ventricular cells, threshold was at -33 mV, maximum at +6 mV and reversal potential at about +50 mV, potentials of half-maximum steady-state inactivation -24 mV and -18 mV. The slopes of steady-state inactivation curves were +4.1 mV in myopathic and +5.5 mV in non-failing cells. In all myocytes the current inactivated with two time constants, a fast one with weak and a slow one with pronounced potential dependency. Ventricular or atrial myocytes from patients pretreated with calcium antagonists and untreated did not differ in current density or steady-state inactivation. Forskolin (0.5 microM) increased calcium currents in myocytes from non-failing and failing hearts to the same extent (by 143 and 150%). While beta-adrenoceptor numbers are reported to decline in severely failing myocardium, our data do not suggest that alterations of the properties of calcium currents contribute to the pathophysiology of heart failure, though the number of investigated hearts is limited due to restricted access to non-failing cardiac tissue. No evidence for impairment of the signal transduction cascade beyond the level of GTP binding proteins was found.

UI MeSH Term Description Entries
D008297 Male Males
D008875 Middle Aged An adult aged 45 - 64 years. Middle Age
D009124 Muscle Proteins The protein constituents of muscle, the major ones being ACTINS and MYOSINS. More than a dozen accessory proteins exist including TROPONIN; TROPOMYOSIN; and DYSTROPHIN. Muscle Protein,Protein, Muscle,Proteins, Muscle
D009206 Myocardium The muscle tissue of the HEART. It is composed of striated, involuntary muscle cells (MYOCYTES, CARDIAC) connected to form the contractile pump to generate blood flow. Muscle, Cardiac,Muscle, Heart,Cardiac Muscle,Myocardia,Cardiac Muscles,Heart Muscle,Heart Muscles,Muscles, Cardiac,Muscles, Heart
D002118 Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Coagulation Factor IV,Factor IV,Blood Coagulation Factor IV,Calcium-40,Calcium 40,Factor IV, Coagulation
D002675 Child, Preschool A child between the ages of 2 and 5. Children, Preschool,Preschool Child,Preschool Children
D005260 Female Females
D005576 Colforsin Potent activator of the adenylate cyclase system and the biosynthesis of cyclic AMP. From the plant COLEUS FORSKOHLII. Has antihypertensive, positive inotropic, platelet aggregation inhibitory, and smooth muscle relaxant activities; also lowers intraocular pressure and promotes release of hormones from the pituitary gland. Coleonol,Forskolin,N,N-Dimethyl-beta-alanine-5-(acetyloxy)-3-ethenyldodecahydro-10,10b-dihydroxy-3,4a,7,7,10a-pentamethyl-1-oxo-1H-naphtho(2,1-b)pyran-6-yl Ester HCl,NKH 477,NKH-477,NKH477
D006325 Heart Atria The chambers of the heart, to which the BLOOD returns from the circulation. Heart Atrium,Left Atrium,Right Atrium,Atria, Heart,Atrium, Heart,Atrium, Left,Atrium, Right
D006333 Heart Failure A heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (VENTRICULAR DYSFUNCTION), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as MYOCARDIAL INFARCTION. Cardiac Failure,Heart Decompensation,Congestive Heart Failure,Heart Failure, Congestive,Heart Failure, Left-Sided,Heart Failure, Right-Sided,Left-Sided Heart Failure,Myocardial Failure,Right-Sided Heart Failure,Decompensation, Heart,Heart Failure, Left Sided,Heart Failure, Right Sided,Left Sided Heart Failure,Right Sided Heart Failure

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