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Regulation of CaV1.2 channels in cardiac myocytes by the β-adrenergic pathway requires a signaling complex in which the proteolytically processed distal C-terminal domain acts as an autoinhibitor of channel activity and mediates up-regulation by the β-adrenergic receptor and PKA bound to A-kinase anchoring protein 15 (AKAP15). We examined the significance(More)
NZB x NZW (NZB x W) F1 hybrid mice spontaneously develop a disease most prominently characterized by immune complex glomerulonephritis (GN), which seems to be associated with both antibodies to DNA and to the serum retroviral envelope glycoprotein, gp70. To evaluate the contribution of each of these autoimmune responses to the pathogenesis of the GN, we(More)
1 Depolarizations were recorded intracellularly in smooth muscle from the taenia of the guinea-pig caecum in response to the iontophoretic application of acetylcholine, carbachol, oxotremorine-M, methylfurmethide, hexyl trimethylammonium and tetramethylammonium (TMA). 2 No differences between the iontophoretic responses to agonists stable to cholinesterase(More)
L-type calcium currents conducted by CaV1.2 channels initiate excitation-contraction coupling in cardiac and vascular smooth muscle. In the heart, the distal portion of the C terminus (DCT) is proteolytically processed in vivo and serves as a noncovalently associated autoinhibitor of CaV1.2 channel activity. This autoinhibitory complex, with A-kinase(More)
1. Membrane potential was recorded intracellularly by micro-electrode in separated longitudinal muscle of guinea-pig ileum. Electrotonic potentials were evoked in longitudinal strips by passing current between large external electrodes in the partition chamber.2. Histamine increased the frequency of action potential discharge at low concentrations and(More)
1. Shortening and rate of loss of (42)K were studied in strips of longitudinal muscle taken from guinea-pig ileum.2. Carbachol, histamine and raising the external potassium concentration, [K(+)](o), to 120 mm in the presence of atropine caused equal maximal shortenings of the muscle, but unequal maximal increases in (42)K efflux: maximal (42)K effluxes(More)
BACKGROUND Mild hypothermia is neuroprotective after cerebral ischemia but surgery involving profound hypothermia (PH, temperature less than 18°C) is associated with neurologic complications. Rewarming (RW) from PH injures hippocampal neurons by glutamate excitotoxicity, N-methyl-D-aspartate receptors, and intracellular calcium. Because neurons are(More)
Patients infected with the human immunodeficiency virus (HIV), and other mammals infected with related lentiviruses, exhibit fatigue, altered sleep patterns, and abnormal circadian rhythms. A circadian clock in the hypothalamic suprachiasmatic nucleus (SCN) temporally regulates these functions in mammals. We found that a secretary HIV transcription factor,(More)
Light information reaches the suprachiasmatic nucleus (SCN) through a subpopulation of retinal ganglion cells. Previous work raised the possibility that brain-derived neurotrophic factor (BDNF) and its high-affinity tropomyosin-related receptor kinase may be important as modulators of this excitatory input into the SCN. In order to test this possibility, we(More)
Using an ethnomedical-based drug discovery program, two previously unknown compounds (SP-18904 and SP-18905) from Pycnanthus angolensis were isolated that lower glucose concentrations in mouse models of type 2 diabetes. SP-18904 and SP-18905 are terpenoid-type quinones that significantly lowered plasma glucose concentration (p <.05) when given orally to(More)