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Biological Research

Print version ISSN 0716-9760


HATORI, EIKI et al. Association of nicotinic acetylcholine receptors with central respiratory control in isolated brainstem-spinal cord preparation of neonatal rats. Biol. Res. [online]. 2006, vol.39, n.2, pp.321-330. ISSN 0716-9760.

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

Keywords : brainstem-spinal cord; neonatal rat; inspiratory neuron; preinspiratory neuron; nicotinic acetylcholine receptor.

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