Mice deficient in the smooth muscle Cav1.2 calcium channel (SMACKO, smooth muscle alpha1c-subunit calcium channel knockout) have a severely reduced micturition and an increased bladder mass. L-type calcium current, protein, and spontaneous contractile activity were absent in the bladder of SMACKO mice. K+ and carbachol (CCh)-induced contractions were reduced to 10-fold in detrusor muscles from ...

This study reports increased intracellular Ca2+ and inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] in response to muscarinic-cholinergic stimulation of human neuroblastoma (SH-SY5Y) cells. Carbachol stimulation leads to a rapid increase in intracellular Ca2+ and Ins(1,4,5)P3 mass, both reaching a peak at around 10 s and then declining to a new maintained phase significantly above basal. Dose-respo...

(-)-[3H]Desmethoxyverapamil ((-)-DMV) binds saturably to homogenates of the osteoblast-like cell lines UMR 106 and ROS 17/2.8 with KD values of 45 and 61 nM and Bmax values of 6.0 and 5 pmol/mg protein, respectively. Binding is stereoselective with (-)-DMV 8-10 times more potent than (+)-DMV. None of the dihydropyridine or benzothiazepine Ca2+ antagonists examined affect (-)-[3H]DMV binding. Mo...

This study investigated the effects of cardiac glycosides on single-channel activity of the cardiac sarcoplasmic reticulum (SR) Ca2+ release channels or ryanodine receptor (RyR2) channels and how this action might contribute to their inotropic and/or toxic actions. Heavy SR vesicles isolated from canine left ventricle were fused with artificial planar lipid bilayers to measure single RyR2 chann...

To determine whether K+-channel activation mediates shear stress-induced pulmonary vasodilation in the fetus, we studied the hemodynamic effects of K+-channel blockers on basal pulmonary vascular resistance and on the pulmonary vascular response to partial compression of the ductus arteriosus (DA) in chronically prepared late-gestation fetal lambs (128-132 days gestation). Study drugs included ...

Transsarcolemmal influx and release from the sarcoplasmic reticulum (SR) through specific Ca2+ channels are the two main pathways to elevate cytosolic Ca2+ (Ca2+i) in vascular smooth muscle cells (VSMCs). To elucidate intercellular distribution and function of the Ca2+ channel in SR in cultured VSMCs, we observed Ca2+i transients by digital two-dimensional imaging with a fluorescent Ca2+ indica...

1. Since the inception of the patch-clamp technique, single-channel recording has made an enormous impact on our understanding of ion channel function and its role in membrane transport and cell physiology. 2. However, the impact of single-channel recording methods on our understanding of intracellular Ca2+ regulation by internal stores is not as broadly recognized. There are several possible r...

Muscle excitation-contraction coupling is, in large part, regulated by the activity of two proteins. These are the ryanodine receptor (RyR), which is an intracellular Ca2+ release channel and the dihydropyridine receptor (DHPR), which is a voltage gated L-type calcium channel. In skeletal muscle, the physical association between RyR1 and L-type Ca2+ channels is required for muscle excitation-co...

Since Ca2+ is a major competitor of protons for the modulation of high voltage-activated Ca2+ channels, we have studied the modulation by extracellular Ca2+ of the effects of proton on the T-type Ca2+ channel alpha1G (CaV3.1) expressed in HEK293 cells. At 2 mM extracellular Ca2+ concentration, extracellular acidification in the pH range from 9.1 to 6.2 induced a positive shift of the activation...

introduction: the ionic currents show nonlinear behavior and electrical stimuli can influence their activation and inactivation kinetics. the time constant of depolarizing or hyperpolarizing current pulses has an important role in the firing behavior of neurons. in the present study, the effects of quasitrpezoidal command potentials on l-type calcium channel of somata of f1 neuron in helix aspe...