Pretreatment of intact rabbit portal vein smooth muscle with the chimeric toxin DC3B (10(-6) M, 48 h; ; ) ADP-ribosylated endogenous RhoA, including cytosolic RhoA complexed with rhoGDI, and inhibited the tonic phase of phenylephrine-induced contraction and the Ca2+-sensitization of force by phenylephrine, endothelin and guanosine triphosphate (GTP)gammaS, but did not inhibit Ca2+-sensitization...

KCl causes smooth muscle contraction by elevating intracellular free Ca2+, whereas receptor stimulation activates an additional mechanism, termed Ca2+ sensitization, that can involve activation of RhoA-associated kinase (ROK) and PKC. However, recent studies support the hypothesis that KCl may also increase Ca2+ sensitivity. Our data showed that the PKC inhibitor GF-109203X did not, whereas the...

BACKGROUND Vasospasm of the spiral modiolar artery (SMA) may cause ischemic stroke of the inner ear. Endothelin-1 (ET-1) induces a strong, long-lasting constriction of the SMA by increasing contractile apparatus Ca2+ sensitivity via Rho-kinase. We therefore tested several Rho-kinase inhibitors and a cell-permeable analogue of cAMP (dbcAMP) for their ability to reverse ET-1-induced constriction ...

Airway smooth muscle cell contraction is regulated by changes in intracellular Ca2+ concentration ([Ca2+]i) and the responsiveness of the airway smooth muscle cell to this Ca2+. The mechanism controlling [Ca2+]i primarily involves agonist-induced release of Ca2+ from internal stores to generate Ca2+ oscillations. The extent of contraction correlates with the persistence and frequency of these C...

KCl has long been used as a convenient stimulus to bypass G protein-coupled receptors (GPCR) and activate smooth muscle by a highly reproducible and relatively "simple" mechanism involving activation of voltage-operated Ca2+ channels that leads to increases in cytosolic free Ca2+ ([Ca2+]i), Ca2+-calmodulin-dependent myosin light chain (MLC) kinase activation, MLC phosphorylation and contraction...

Little is known about the signaling pathways involved in alpha 2-adrenergic receptor-mediated contraction of vascular smooth muscle. In the present study, we measured intracellular Ca2+ ([Ca2+]i), myosin light chain (MLC) phosphorylation, and myofilament Ca2+ sensitivity during stimulation with the relatively selective alpha 2-agonist UK 14304. These effects were compared and contrasted with co...

4-Aminopyridine (4-AP), a compound usually known as a K(+)-channel inhibitor, induced rapid cytosolic alkalinization from pH 7.15 to pH 7.4, and subsequently Ca2+ mobilization in the T-lymphocyte cell line Jurkat. Other weak bases, such as NH4Cl or triethanolamine, induced a smaller and/or slower increase in cytosolic pH, resulting in a lower or no detectable Ca2+ signal. In the presence of ext...

Cardiomyocyte Ca2+ dictates cardiac contraction via excitation–contraction coupling (ECC) and excitation–transcription coupling. Adaptation to these processes also majorly contributes enhanced contractile function capacity following exercise training. Cytoplasmic release controls sarcomeric contraction, with important modulation by the voltage-sensitive plasma membrane L-type channel Ryanodine ...