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The posttranscriptional mechanisms that control the cycling of circadian clock protein levels are not known. Here we demonstrate a role for protein phosphatase 2A (PP2A) in the cyclic expression of the PER protein. PP2A regulatory subunits TWS and WDB target PER and stabilize it in S2 cells. In adult fly heads, expression of tws cycles robustly under(More)
Ca2+ sparks, the elementary units of sarcoplasmic reticulum (SR) Ca2+ release in cardiac, smooth and skeletal muscle are localized (2-4 microns ) increases in intracellular Ca2+ concentration, [Ca2+]i, that last briefly (30-100 ms). These Ca2+ sparks arise from the openings of a single SR Ca2+ release channel (ryanodine receptor, RyR) or a few RyRs acting(More)
Calcium entry through voltage-gated Ca2+ channels is critical in cardiac excitation-contraction coupling and calcium metabolism. In this report, we demonstrate both spatially resolved and temporally distinct effects of Ca2+/calmodulin-dependent protein kinase II (CaMKII) on L-type Ca2+ channel current (ICa) in rat cardiac myocytes. Either depolarization(More)
Cardiac beating arises from the spontaneous rhythmic excitation of sinoatrial (SA) node cells. Here we report that SA node pacemaker activity is critically dependent on Ca(2+)/calmodulin-dependent protein kinase II (CaMKII). In freshly dissociated rabbit single SA node cells, inhibition of CaMKII by a specific peptide inhibitor, autocamtide-2 inhibitory(More)
Efficient excitatory transmission depends on a family of transporters that use the Na(+)-electrochemical gradient to maintain low synaptic concentrations of glutamate. These transporters consume substantial energy in the spatially restricted space of fine astrocytic processes. GLT-1 (EAAT2) mediates the bulk of this activity in forebrain. To date,(More)
A plausible determinant of the specificity of receptor signaling is the cellular compartment over which the signal is broadcast. In rat heart, stimulation of beta(1)-adrenergic receptor (beta(1)-AR), coupled to G(s)-protein, or beta(2)-AR, coupled to G(s)- and G(i)-proteins, both increase L-type Ca(2+) current, causing enhanced contractile strength. But(More)
To elucidate microscopic mechanisms underlying the modulation of cardiac excitation-contraction (EC) coupling by beta-adrenergic receptor (beta-AR) stimulation, we examined local Ca(2+) release function, ie, Ca(2+) spikes at individual transverse tubule-sarcoplasmic reticulum (T-SR) junctions, using confocal microscopy and our recently developed technique(More)
The effects of beta 2- and beta 1-adrenoceptor (beta 2AR and beta 1AR, respectively) agonists on the cytosolic Ca2+ (Cai) transient (indexed by the transient increase in indo-1 fluorescence ratio after excitation), twitch amplitude (measured via photodiode array), membrane potential, and L-type sarcolemmal Ca2+ current (ICa, measured by whole-cell patch(More)
1. The nature of the signal that terminates the release of Ca2+ from the cardiac sarcoplasmic reticulum has remained elusive. This study was intended to examine whether FK506-binding protein (FKBP), which is tightly associated to the ryanodine receptor (RyR)/Ca2+ release channel, plays a role in the termination of Ca(2+)-induced Ca2+ release (CICR) in(More)
The nuclear hormone receptor constitutive androstane receptor (CAR, NR1I3) regulates detoxification of xenobiotics and endogenous molecules, and has been shown to be involved in the metabolism of hepatic bile acids and cholesterol. The goal of this study was to address potential effects of CAR on the metabolism of HDL particles, key components in the(More)