Although previous in vivo recording studies in rodents have demonstrated profound decreases in the firing activity of ventral tegmental area (VTA) dopamine neurons after withdrawal from long-term ethanol exposure, the cellular mechanisms underlying this reduced activity are not well understood. Somatodendritic dopamine release within the VTA exerts powerful feedback inhibition of dopamine neuron activity via stimulation of D-2 autoreceptors and subsequent activation AZD1080 of G protein-gated inwardly rectifying K+ (GIRK) channels. Here, by performing patch-clamp recordings from putative dopamine neurons in the VTA of mouse brain slices, we show that D-2 receptor/GIRK-mediated
inhibition becomes more potent and exhibits less desensitization after withdrawal from repeated in vivo ethanol exposure (2 g/kg, i.p., three times daily for 7 days). In contrast, GABA(B) receptor/GIRK-mediated inhibition selleck chemicals and its desensitization are not affected. Chelating cytosolic Ca2+ with BAPTA augments D-2 inhibition and suppresses its desensitization in control mice, while these effects of BAPTA are occluded in ethanol-treated mice. Furthermore, inositol 1,4,5-trisphosphate
(IP3)-induced intracellular Ca2+ release and Ca2+/calmodulin-dependent protein kinase II are selectively involved in the desensitization of D-2, but not GABA(B), receptor signaling. Consistent with this, activation of metabotropic glutamate receptors that are coupled to IP3 generation leads to cross-desensitization of D-2/GIRK-mediated
responses. We propose that enhancement of D-2 receptor-mediated autoinhibition via attenuation of a Ca2+-dependent desensitization mechanism may contribute to the hypodopaminergic state during ethanol withdrawal. Neuropsychopharmacology (2011) 36, 993-1002; doi:10.1038/npp.2010.237; published online 19 MX69 in vitro January 2011″
“Objective: The objective of the present study was to evaluate the utility of tissue Doppler imaging for predicting the development of postoperative atrial fibrillation.
Methods: In this prospective observational study, we evaluated 126 patients with lung cancer who underwent a lobectomy during the 18-month period from August 2007 to January 2009. Preoperative evaluations for all patients included tissue Doppler imaging in addition to conventional echocardiographic analysis. The study end point was the development of postoperative atrial fibrillation.
Results: Postoperative atrial fibrillation was identified in 29 (23%) patients, in whom significantly higher early transmitral velocity/tissue Doppler mitral annular early diastolic velocity values were noted compared with those seen in patients without atrial fibrillation (9.76 +/- 2.3 vs 7.14 +/- 1.7, P < .0001).