Association of nicotinic acetylcholine receptors with central respiratory control in isolated brainstem-spinal cord preparation of neonatal rats

Nicotine exposure is a risk factor in several breathing disorders Nicotinic acetylcholine receptors (nAChRs) exist in the ventrolateral medulla, an important site for respiratory control. We examined the effects of nicotinic acetylcholine neurotransmission on central respiratory control by addition of a nAChR agonist or one of various antagonists into superfusion medium in the isolated brainstem-spinal cord from neonatal rats. Ventral C4 neuronal activity was monitored as central respiratory output, and activities of respiratory neurons in the ventrolateral medulla were recorded in whole-cell configuration. RJR-2403 (0.1-10mM), a4b2 nAChR agonist induced dose-dependent increases in respiratory frequency. Non-selective nAChR antagonist mecamylamine (0.1-100mM), a4b2 antagonist dihydro-b-erythroidine (0.1-100mM), a7 antagonist methyllycaconitine (0.1-100mM), and a-bungarotoxin (0.01-10mM) all induced dose-dependent reductions in C4 respiratory rate. We next examined effects of 20mM dihydro-b-erythroidine and 20mM methyllycaconitine on respiratory neurons. Dihydro-b-erythroidine induces hyperpolarization and decreases intraburst firing frequency of inspiratory and preinspiratory neurons. In contrast, methyllycaconitine has no effect on the membrane potential of inspiratory neurons, but does decrease their intraburst firing frequency while inducing hyperpolarization and decreasing intraburst firing frequency in preinspiratory neurons. These findings indicate that a4b2 nAChR is involved in both inspiratory and preinspiratory neurons, whereas a7 nAChR functions only in preinspiratory neurons to modulate C4 respiratory rate.

Sleep apnea syndrome among patients with hypothyroidism.

OBJECTIVE: There is an association of sleep apnea among patients with untreated hypothyroidism. Thyroxine therapy is considered to reduce AHI (apnea-hypopnea index) significantly. A study of 20 successive hypothyroid patients was undertaken to investigate the occurrence of sleep apneas, and response to thyroxine therapy after achieving euthyroid state. METHODS: Sleep studies were conducted in 20 consecutive hypothyroid patients at our sleep centre while they were hypothyroid. All were restudied during euthyroid state subsequent to three months of thyroxine therapy. RESULTS: Nine (45%) of untreated 20 patients had obstructive sleep apnea syndrome (OSAS). Restudy of them during euthyroid state showed complete recovery in six, partial improvement in two and no change in one. Besides them, three other patients developed sleep apnea syndrome of central origin after euthyroid state was achieved. Central respiratory drive improved in 17 patients, while it was reduced among three of nine patients with OSAS who did not show recovery. CONCLUSION: Our experience suggests that there is high incidence of sleep apnea among hypothyroid patients. Thyroxine treatment could achieve disappearance of these apneas in majority of them. Few hypothyroids may develop sleep apnea despite the achievement of euthyroid state. Central respiratory drive probably plays an insignificant role in the pathogenesis of sleep apnea among hypothyroids.