Αρχειοθήκη ιστολογίου

Τετάρτη 23 Αυγούστου 2017

Functional and molecular plasticity of gamma and alpha-1 GABAA receptor subunits in the dorsal motor nucleus of the vagus after experimentally-induced diabetes

Chronic experimentally-induced hyperglycemia augments subunit specific gamma-aminobutyric acid A (GABAA) receptor-mediated inhibition of parasympathetic preganglionic motor neurons in the dorsal motor nucleus of the vagus (DMV). However, the contribution of α1 or GABAA receptor subunits, which are ubiquitously expressed on central nervous system neurons, to this elevation in inhibitory tone have not been determined. This study investigated the effect of chronic hyperglycemia/hypoinsulinemia on α1- and -subunit specific GABAA receptor-mediated inhibition using electrophysiological recordings in vitro and quantitative (q)RT-PCR. DMV neurons from streptozotocin-treated mice demonstrated enhancement of both phasic and tonic inhibitory currents in response to application of the α1-subunit selective GABAA receptor positive allosteric modulator, zolpidem. Responses to low concentrations of the GABAA receptor antagonist, gabazine suggested an additional increased contribution of -subunit-containing receptors to tonic currents in DMV neurons. Consistent with the functional elevation in α1- and -subunit-dependent activity, transcription of both the α1- and 2-subunits was increased in the dorsal vagal complex of streptozotocin-treated mice. Overall these findings suggest an increased sensitivity to both zolpidem and gabazine after several days of hyperglycemia/hypoinsulinemia, which could contribute to altered parasympathetic output from DMV neurons in diabetes.



from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2vqueA5

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