Possible Role of TRP Channels in Rat Glomus Cells
Carotid body (CB) glomus cells depolarize in response to hypoxia, causing a [Ca2+]i increase, at least in part, through activation of voltage-dependent channels. Recently, Turner et al. (2013) showed that mouse glomus cells with knockout of TASK1/3−/− channels have near-normal [Ca2+]i response to hypoxia. Thus, we postulated that TRP channels may provide an alternate calcium influx pathway which may be blocked by the TRP channel antagonist, 2-APB (2-aminoethoxydiphenylborane). We confirmed that 2-APB inhibited the afferent nerve response to hypoxia, as previously reported (Lahiri S, Patel G, Baby S, Roy A (2009) 2-APB mediated effects on hypoxic calcium influx in rat carotid body glomus cells. FASEB 2009, Abstract, LB157; Kumar P, Pearson S, Gu Y (2006) A role for TRP channels in carotid body chemotransduction? FASEB J 20:A12–29). To examine the mechanism for this inhibition, we examined dissociated rat CB glomus cells for [Ca2+]i responses to hypoxia, anoxia (with sodium dithionite), 20 mM K+, NaSH, NaCN, and FCCP in absence/presence of 2-APB (100 μM). Also the effect of 2-APB on hypoxia and/or anoxia were investigated on NADH and mitochondria (MT) membrane potential. Our findings are as follows: (1) 2-APB significantly blocked the [Ca2+]i increase in response to hypoxia and anoxia, but not the responses to 20 mM K+. (2) The [Ca2+]i responses NaSH, NaCN, and FCCP were significantly blocked by 2-APB. (3) Hypoxia-induced increases in NADH/NAD+ and MT membrane depolarization were not effected by 2-APB. Thus TRP channels may provide an important pathway for calcium influx in glomus cells in response to hypoxia.
KeywordsCarotid body Glomus cells TRP channels 2-APB [Ca2+]i NADH/NAD+ Mitochondria (MT) membrane potential
This study was supported by Dr. Carroll FY13 SAF Bridging fund and ABI Project fund from ACHRI.
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