| Autor: |
Mokashi A; Department of Physiology, University of Pennsylvania Medical Center, Philadelphia, PA, USA., Roy A; Department of Physiology and Pharmacology, University of Calgary, Calgary, Canada., Baby SM; Department of Drug Discovery, Galleon Pharmaceuticals, Inc., Horsham, PA, USA., Mulligan EM; Pennsylvania State University, Altoona, PA, USA., Lahiri S; Department of Physiology, University of Pennsylvania Medical Center, Philadelphia, PA, USA., Di Giulio C; Department of Neurosciences Imaging and Clinical Sciences, University of Chieti-Pescara, Chieti, Italy., Pokorski M; Institute of Health Sciences, University of Opole, Opole, Poland. m_pokorski@hotmail.com. |
| Abstrakt: |
This article addresses the disparity in the transduction pathways for hypoxic and hypercapnic stimuli in carotid body glomus cells. We investigated and reviewed the experimental evidence showing that the response to hypoxia, but not to hypercapnia, is mediated by 1,4,5-inositol triphosphate receptors (IP 3 R/s) regulating the intracellular calcium content [Ca 2+ ] c in glomus cells. The rationale was based on the past observations that inhibition of oxidative phosphorylation leads to the explicit inhibition of the hypoxic chemoreflex. [Ca 2+ ] c changes were measured using cellular Ca 2+ -sensitive fluorescent probes, and carotid sinus nerve (CSN) sensory discharge was recorded with bipolar electrodes in in vitro perfused-superfused rat carotid body preparations. The cell-permeant, 2-amino-ethoxy-diphenyl-borate (2-APB; 100 μM) and curcumin (50 μM) were used as the inhibitors of IP 3 R/s. These agents suppressed the [Ca 2+ ] c , and CSN discharge increases in hypoxia but not in hypercapnia, leading to the conclusion that only the hypoxic effects were mediated via modulation of IP 3 R/s. The ATP-induced Ca 2+ release from intracellular stores in a Ca 2+ -free medium was blocked with 2-APB, supporting this conclusion. |
