Brainstem NHE-3 Expression and Control of Breathing

Intracellular acidification by selective inhibition of the Na⁺/H⁺ exchanger type 3 (NHE-3) has been shown to enhance the bioelectric activity of CO₂/H⁺ sensitive neurons cultured in vitro from the ventrolateral medulla oblongata of newborn rats (Wiemann et al., 1998, 1999; Wiemann and Bingmann, 2001). Recently, we demonstrated NHE-3 immunoreactive neurons in brainstem areas with prevalence for central chemosensitivity in adult rabbits (Kiwull-Schöne et al., 2001). During anaesthesia, NHE-3 inhibition by the brain-permeant substance S8218 (Aventis Pharma) significantly lowered the arterial threshold PCO₂ for central apnea upon mechanical hyperventilation, both under normal blood gas conditions and after prolonged respiratory acidosis (Kiwull-Schöne et al., 2001, 2003). This could be of clinical importance, since there is evidence that increased Na⁺/H⁺ antiporter (NHE) activity may predispose patients to sleep apnea (Tepel et al., 2000).