Expression of Neuronal Nitric Oxide Synthase in Rabbit Carotid Body Glomus Cells Regulates Large-Conductance Ca²⁺-Activated Potassium Currents

Abstract

Li Y-L, Zheng H, Ding Y, Schultz HD. Expression of neuronal nitric oxide synthase in rabbit carotid body glomus cells regulates large-conductance Ca 2ϩ -activated potassium currents. J Neurophysiol 103: 3027-3033, 2010. First published March 31, 2010 doi:10.1152/jn.01138.2009. Our previous studies show that a decrease in endogenous nitric oxide (NO) is involved in the blunted outward K ϩ currents in carotid body (CB) glomus cells from chronic heart failure (CHF) rabbits. In the present study, we measured the effects of the neuronal nitric oxide synthase (nNOS) transgene on the K ϩ currents in CB glomus cells from pacing-induced CHF rabbits. Using single-cell real-time RT-PCR and immunofluorescent techniques, we found that nNOS mRNA and protein are expressed in the rabbit CB glomus cells and CHF decreased the expression of nNOS mRNA and protein in CB glomus cells. After 3 days of an adenoviral nNOS (Ad.nNOS) gene transfection, the expression of nNOS protein was increased to the level found in sham CB glomus cells. In whole cell patch-clamp experiments, Ad.nNOS markedly reversed the attenuated K ϩ currents in CB glomus cells from CHF rabbits. The specific nNOS inhibitor (S-methyl-L-thiocitrulline [SMTC]) and large-conductance Ca 2ϩ -activated K ϩ (BK) channel blocker (iberiotoxin) fully abolished the effect of Ad.nNOS on the K ϩ currents in the CB glomus cells from CHF rabbits. However, neither CHF nor Ad.nNOS altered the protein expression of BK channel ␣-subunit. These results suggest that a decrease of NO induced by an attenuated nNOS activity lowers the activation of the BK channels but not the protein expression of the BK channel ␣-subunit in the CB glomus cells during CHF.

Morphological differences of the carotid body among C57/BL6 (B6), A/J, and CSS B6A1 mouse strains

“…Nitric oxide (NO) is a messenger molecule involved in the regulation of respiration and specifically with neuronal NOS having been shown, in part, to influence the respiratory response to hypoxia and reoxygenation in the mouse (Kline et al, 1998; Price et al, 2003). Its presence in type I cells is not unprecedented (Dvorakova and Kummer, 2005; Li et al, 2010; Leite et al, 2010). Type I cells are derived from neural crest (Pearse et al, 1973).…”

Ventilatory behavior and carotid body morphology of Brown Norway and Sprague Dawley rats

“…However, it is possible that the BN do indeed possess greater than or similar CB afferent activity in relation to the SD, but such afferent activity is simply processed differently in the medulla. Nerve recording from the isolated and severed carotid sinus nerve can be used to measure afferent activity of the CB in response to hypoxia (Li et al, 2010). Such a technique could be used to compare CB activity of the SD and BN, isolating CB functions from those of central processing for respiratory control.…”

“…Both Dejours phenomenon and PHFD were absent in the SD with vehicle administration (Subramanian et al, 2002). There are several studies examining nNOS protein expression in the carotid body but none describing strain differences (Dvorakova and Kummer, 2005; Leite et al, 2010; Li et al, 2010). …”

Role of the Carotid Body in the Pathophysiology of Heart Failure

“…NO suppresses CB chemoreceptor discharge in normoxic conditions because O 2 is essential for biosynthesis of NO [14]. Basal NO production and nNOS/eNOS expression within the CB are depressed in CHF [18, 28, 11]. Thus, the tonic inhibitory effect of NO on the activity of CB chemoreceptors and its enhancement of I Kv in glomus cells under normoxic conditions are virtually absent in CHF rabbits [21] Adenoviral gene transfer of nNOS to the CB in CHF rabbits reverses the enhanced resting CB chemoreceptor activity seen in the CHF state and reduces resting renal sympathetic nerve activity [17].…”