Regulation of the slow Ca++ channels of myocardial cells

Abstract

Contraction of the heart is regulated by a number of mechanisms, such as neurotransmitters, hormones, autacoids, pH, intracellular ATP, and Ca++ ions. These actions are mediated, at least in part, by actions on the sarcolemmal slow (L-type) Ca++ channels, exerted directly or indirectly. The major mechanisms for the regulation of the slow Ca++ channels of myocardial cells includes the following. cAMP/PK-A phosphorylation stimulates the slow Ca++ channel activity, whereas cGMP/PK-G phosphorylation inhibits. DAG/PK-C phosphorylation and tyrosine kinase phosphorylation are suggested to stimulate the slow Ca++ channel activity. Intracellular application of Gs alpha protein increases the slow Ca++ currents (ICa(L)). Lowering of intracellular ATP inhibits ICa(L). Acidosis and increase in [Ca]i inhibits ICa(L). A number of changes in the Ca++ channels also occur during development and aging. Thus, it appears that the slow Ca++ channel is a complex structure, including perhaps several associated regulatory proteins, which can be regulated by a number of extrinsic and intrinsic factors, and thereby control can be exercised over the force of contraction of the heart.

Regulation of Cardiac L-Type Ca 2+ Channel Ca V 1.2 Via the β-Adrenergic-cAMP-Protein Kinase A Pathway

“…Early works, corroborated by many recent studies, found a β-AR-induced activation of AC followed by a rise in cAMP in the heart and in cultured cardiomyocytes, showed enhancement of L-VDCC currents in cardiomyocytes by cAMP, PKA-CS, phosphodiesterase, and protein phosphatase inhibitors, and demonstrated negation of these effects by protein phosphatases 12,18,21,60,61 . Purified PKA-CS has been shown to activate purified Ca V 1.1 (the L-VDCC of the skeletal muscle) and cardiac Ca V 1.2, after reconstitution in lipid bilayers and liposomes [62][63][64][65][66] suggesting that the target for PKA regulation is the channel itself.…”

“…100 Some of the results obtained in excised patches or in perfused cells that seemed to support the direct effect of G proteins could be because of a partial relief of Mg 2+ inhibition 101 or of channel rundown in ATP-free solutions used. 60,102 to propose the hypothesis, which became quite popular and was supported by studies in other cell types 103 that the L-VDCC needs to be basally phosphorylated by PKA to become functional. However, smaller or no effects on basal I Ca were seen in later works that used cell dialysis of inhibitors through the patch pipette or extracellular incubation with cell-permeable inhibitors.…”

Increased sympathetic activity can cause repolarization instability in athlete's heart

“…The increased sympathetic tone causes elevated cathecolamine levels. This effect in athletes can enhance susceptibility to arrhythmia by increasing both trigger activity (extrasystoles) [5][6][7] and arrhythmia substrate (repolarization inhomogeneity) [8][9][10].…”

“…The increased sympathetic tone causes elevated cathecolamine levels. This effect in athletes can enhance susceptibility to arrhythmia by increasing both trigger activity (extrasystoles) [5][6][7] and arrhythmia substrate (repolarization inhomogeneity) [8][9][10].As the ECG leads show the regional electrical activity of myocardium, the difference between QT intervals and the QT-dispersion gives information about spatial inhomogeneity of repolarisation [11,12].Our aim in this study was to investigate the correlation between the sympathetic tone and the repolarization instability in different sports and in non-trained healthy controls. Phone: +3620/825-0263; E-mail: komkazsolt@gmail.com Abstract: Sudden cardiac death (SCD) of athletes usually occurs during warm-up or shortly after training.…”

Analysis of short-term temporal variability of cardiac ventricular repolarization in subjects with different clinical conditions

“…Non-steroid antiinflammatory drugs are used by athletes very often and in large doses to treat sports injuries. These factors can create and enhance the arrhythmia substrate in athletes, while elevated intracellular cAMP levels due to increased sympathetic disharge may contribute to trigger extrasystole generation via increased pacemaker (I f ) current [49] and/or increased L-type calcium current [50].…”