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Large conductance voltage- and Ca(2+)-activated potassium channels (BK channels) are important feedback regulators in excitable cells and are potently regulated by protein kinases. The present study reveals a dual role of protein kinase C (PKC) on BK channel regulation. Phosphorylation of S(695) by PKC, located between the two regulators of K(+) conductance(More)
Large-conductance, calcium- and voltage-gated potassium (BK) channels play an important role in cellular excitability by controlling membrane potential and calcium influx. The stress axis regulated exon (STREX) at splice site 2 inverts BK channel regulation by protein kinase A (PKA) from stimulatory to inhibitory. Here we show that palmitoylation of STREX(More)
1. The inotropic effects of (±)-isoprenaline and several phosphodiesterase (PDE)-inhibitors were studied in isometrically contracting guinea-pig papillary muscles driven at a rate of 0.2 Hz. The maximal positive inotropic effect of isoprenaline (ΔF c=2.2 g;n=7) corresponded to that of 1-methyl, 3-isobutylxanthine (IBMX) and theophylline (ΔF c=2.1 and 2.2 g,(More)
The aim of the present study was to determine the mechanism of the positive inotropic effect of carbachol on ventricular myocardium. Carbachol produced a concentration-dependent (0.1 to 300 μmol/l) increase in contraction force on the catecholamine-depleted papillary muscle of the guinea pig without affecting the normal action potential or the slow action(More)
1. The inotropic effects of benzyl-and substituted benzyl triesters of cyclic AMP and cyclic GMP were studied in isometrically contracting guineapig papillary muscles driven at a rate of 0.2 Hz. 2. The triesters of cyclic AMP produced marked concentration-dependent positive inotropic effects. The maximum increase of contraction force (ΔF c) was 2.2 g (n=5)(More)
BACKGROUND Abnormally elevated blood pressure is the most prevalent risk factor for cardiovascular disease. The large-conductance, voltage- and Ca2+-dependent K+ (BK) channel has been proposed as an important effector in the control of vascular tone by linking membrane depolarization and local increases in cytosolic Ca2+ to hyperpolarizing K+ outward(More)
Airway smooth muscle is richly endowed with muscarinic receptors of the M(2) and M(3) subtype. Stimulation of these receptors inhibits large conductance calcium-activated K(+) (BK) channels, a negative feed back regulator, in a pertussis toxin-sensitive manner and thus facilitates contraction. The underlying mechanism, however, is unknown. We therefore(More)
The inotropic potencies of 8-substituted cyclic AMP analogues, applied as sodium salts and in form of benzyl esters, were determined in isolated guinea-pig papillary muscles contracting isometrically at a frequency of 0.2 Hz. 1. Half-maximally effective concentrations, EC50, for the positive inotropic effect of 8-substituted cyclic AMP (sodium salt)(More)
Regulation of protein phosphorylation by kinases and phosphatases is involved in many signaling pathways in mammalian cells. In contrast to prokaryotes and lower eukaryotes a role for the reversible phosphorylation of histidine residues is just emerging. The β subunit of heterotrimeric G proteins, the metabolic enzyme adenosine 5'-triphosphate-citrate lyase(More)
The large-conductance, voltage-dependent and Ca(2+)-dependent K(+) (BK) channel links membrane depolarization and local increases in cytosolic free Ca(2+) to hyperpolarizing K(+) outward currents, thereby controlling smooth muscle contractility. Constitutive deletion of the BK channel in mice (BK(-/-)) leads to an overactive bladder associated with(More)