Prolonged exhaustive submaximal exercise in humans induces marked metabolic changes, but little is known about effects on muscle Na+-K+-ATPase activity and sarcoplasmic reticulum Ca2+ regulation. We therefore investigated whether these processes were impaired during cycling exercise at 74.3 +/- 1.2% maximal O2 uptake (mean +/- SE) continued until fatigue in eight healthy subjects (maximal O2 up...

Most neurons fire in bursts, imposing episodic energy demands, but how these demands are coordinated with oxidative phosphorylation is still unknown. Here, using fluorescence imaging techniques on presynaptic termini of Drosophila motor neurons (MNs), we show that mitochondrial matrix pH (pHm), inner membrane potential (Δψm), and NAD(P)H levels ([NAD(P)H]m) increase within seconds of nerve stim...

Increases in intraluminal shear stress are thought to cause vasodilation of coronary arterioles by activation of Ca2+-dependent endothelial nitric oxide synthase followed by release of nitric oxide. We tested the hypothesis that endothelium-dependent vasodilation of isolated coronary arterioles to shear stress and agonists is necessarily preceded by an increase in endothelial cell Ca2+concentra...

To determine platelet Ca2+ transport entities involved in increased cytosolic Ca2+ in the platelets of hypertensive individuals, we studied the relations between blood pressure and Ca2+ transporters in platelet membranes from 22 white male volunteers 32 to 68 years old. We used thapsigargin, a specific inhibitor of the internal membrane Ca(2+)-ATPase, to differentiate between plasma membrane an...

Nomura, Noriyuki, Hiroshi Satoh, Hajime Terada, Masaki Matsunaga, Hiroshi Watanabe, and Hideharu Hayashi. CaMKII-dependent reactivation of SR Ca2 uptake and contractile recovery during intracellular acidosis. Am J Physiol Heart Circ Physiol 283: H193–H203, 2002; 10.1152/ ajpheart.00026.2001.—In hearts, intracellular acidosis disturbs contractile performance by decreasing myofibrillar Ca2 respon...

A decrease in the myocardial level of the mRNA encoding the Ca2(+)-ATPase of the sarcoplasmic reticulum (SR) has been recently reported during experimental cardiac hypertrophy and failure. To determine if such a deficit occurs in human end-stage heart failure, we compared the SR Ca2(+)-ATPase mRNA levels in left (LV) and right ventricular (RV) specimens from 13 patients undergoing cardiac trans...

Ca2+ channels display remarkable selectivity and permeability, traditionally attributed to multiple, discrete Ca2+ binding sites lining the pore. Each of the four pore-forming segments of Ca2+ channel alpha 1 subunits contains a glutamate residue that contributes to high-affinity Ca2+ interactions. Replacement of all four P-region glutamates with glutamine or alanine abolished micromolar Ca2+ b...

The reduction in Ca2+ concentration during diastole and relaxation occurs differently in normal hearts and in hypertrophied hearts secondary to pressure overload. We have studied some possible molecular mechanisms underlying these differences by examining the function of the sarcoplasmic reticulum and the expression of the gene encoding its Ca2(+)-ATPase in rat hearts with mild and severe compe...

OBJECTIVE Sarcoplasmic reticulum dysfunction may contribute to calcium (Ca2+) overload during myocardial reperfusion. The aim of this study was to investigate its role in reperfusion injury. METHODS Open chest dogs undergoing 15 min of left anterior descending coronary artery occlusion and 3 h of reperfusion were randomized to intracoronary infusions of 0.9% saline, vehicle, or the Ca2+ chann...

The use of digitonin to permeabilize Trypanosoma cruzi plasma membrane enabled us to study Ca2+ transport and oxidative phosphorylation in mitochondria in situ. Addition of Ca2+ to these preparations evoked a cycle of respiratory stimulation. Ca2+ uptake was partially inhibited by ruthenium red, almost totally inhibited by antimycin A, and stimulated by inorganic phosphate. Addition of carbonyl...