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Chemosensing at the carotid body. Involvement of a HERG-like potassium current in glomus cells.

Currently, it is not clear what type of K+ channel(s) is active at the resting membrane potential (RMP) in glomus cells of the carotid body (CB). HERG channels produce currents that are known to contribute to the RMP in other neuronal cells. The goal of the present study was to determine whether CB glomus cells express HERG-like (HL) K+ current, and if so, to determine whether HL currents regulate the RMP. With high [K+]o, depolarizing voltage steps from -85 mV revealed a slowly deactivating inward tail current indicative of HL K+ current in whole-cell, voltage clamped glomus cells. The HL currents were blocked by dofetilide (DOF) in a concentration-dependent manner (IC50 = 13 nM) and high concentrations (1 and 10 mM) of Ba2+. The steady-state activation properties of the HL current (Vh = -45 mV) suggest that it is active at the RMP in glomus cells. Whole-cell, current clamped glomus cells exhibited a RMP of -48 mV. 150 nM DOF caused a significant (14 mV) depolarizing shift in the RMP. In isolated glomus cells, [Ca2+]i increased in response to DOF (1 microM). In an in-vitro CB preparation, DOF increased basal sensory discharge in a concentration-dependent manner and significantly attenuated the sensory response to hypoxia. These results suggest that the HERG-like current is responsible for controlling the RMP in glomus cells of the rabbit CB, and that it is involved in the chemosensory response to hypoxia of the CB.

Animals↗

Response of intracellular pH to acute anoxia in individual neurons from chemosensitive and nonchemosensitive regions of the medulla.

The effect of acute (10 minutes) exposure to anoxia on intracellular pH (pHi) in individual brainstem neurons, in slices from neonatal (P7 to P11) rats, was studied using a fluorescence microscopy imaging technique. Neurons from 4 regions of the medulla were studied, two of which contained chemosensitive neurons (nucleus tractus solitarius, NTS, and ventrolateral medulla, VLM) and two regions which did not contain chemosensitive neurons (hypoglossal, Hyp, and inferior olivary, IO). Acute anoxia caused a rapid and maintained acidification of 0.1-0.3 pH unit that was not different in neurons from chemosensitive vs. nonchemosensitive regions. Blocking the contribution of Na+/H+ exchange (NHE) to pHi regulation by exposing neurons to acute anoxia in the presence of the exchange inhibitor amiloride (1 mM) did not affect the degree of acidification seen in neurons from the NTS and VLM region, but significantly increased acidification (to about 0.35 pH unit) in Hyp and IO neurons. In summary, anoxia-induced intracellular acidification is not different between neurons from chemosensitive and nonchemosensitive regions, but NHE activity blunts acidification in neurons from the latter regions. These data suggest that neurons from chemosensitive areas might have a smaller acid load in response to anoxia than neurons from nonchemosensitive regions of the brainstem.

Amiloride↗