Noradrenergic modulation of XII motoneuron inspiratory activity does not involve α₂-receptor inhibition of theI_hcurrent or presynaptic glutamate release

Abstract

. Noradrenergic modulation of XII motoneuron inspiratory activity does not involve ␣ 2-receptor inhibition of the Ih current or presynaptic glutamate release. J Appl Physiol 98: 1297 -1308 ,2005 .FirstpublishedDecember3,2004doi:10.1152/japplphysiol. 00977.2004.-Norepinephrine has powerful and diverse modulatory effects on hypoglossal (XII) motoneuron activity, which is important in maintaining airway patency. The objective was to test two hypotheses that ␣ 2-adrenoceptor-mediated, presynaptic inhibition of glutamatergic inspiratory drive (Selvaratnam SR, Parkis MA, and Funk GD. Brain Res 805: 104 -115, 1998) and postsynaptic inhibition of the hyperpolarization-activated inward current (I h) (Parkis MA and Berger AJ. Brain Res 769: 108 -118, 1997) modulate XII inspiratory activity. Nerve and whole cell recordings were applied to rhythmic medullary slice preparations from neonatal rats (postnatal days 0 -4) to monitor XII inspiratory burst amplitude and motoneuron properties. Application of an ␣ 2-receptor agonist (clonidine, 1 mM) to the XII nucleus reduced inspiratory burst amplitude to 71 Ϯ 3% of control but had no effect on inspiratory synaptic currents. It also reduced the I h current by ϳ40%, but an Ih current blocker (ZD7288), at concentrations that blocked ϳ80% of Ih, had no effect on inspiratory burst amplitude. The clonidine inhibition was unaffected by the GABAA antagonist (ϩ)bicuculline but attenuated by the ␣2-antagonist rauwolscine and the imidazoline 1 (I1) antagonist efaroxan. The I1 agonist rilmenidine, but not the ␣2-agonist UK14304, inhibited XII output. Clonidine also reduced action potential amplitude or impaired repetitive firing. Although a contribution from ␣ 2, and in particular I1, receptors remains possible, results demonstrate that 1) noradrenergic modulation of XII inspiratory activity is unlikely to involve ␣ 2-receptor-mediated presynaptic inhibition of glutamate release or modulation of I h; 2) inhibition of repetitive firing is a major factor underlying the inhibition of XII output by clonidine; and 3) Ih is present in neonatal XII motoneurons but does not contribute to shaping their inspiratory activity. airway control; ␣2-adrenoceptor; hyperpolarization-activated inward current; whole cell recording; rat; clonidine HYPOGLOSSAL (XII) motoneurons contribute to a number of rhythmic motor behaviors that are functional from the time of birth including swallowing, coughing, chewing, and vocalization (4, 53). They also play an important role in breathing whereby they help to maintain upper airway patency during inspiration by increasing genioglossus muscle tone. Their critical role in maintaining airway patency and the fact that airway dysfunction during sleep is implicated in obstructive sleep apnea and some cases of sudden infant death syndrome, combined with their utility for examining basic questions of signal processing, underlie the intense interest in understanding the neuromodulatory control of XII motoneuron excitability (18,45,52,55,62).Noradrenergic signaling cascades, for...

Adrenergic Receptors Modulate Motoneuron Excitability, Sensory Synaptic Transmission and Muscle Spasms After Chronic Spinal Cord Injury

“…Additionally, ␣ 2 receptors may be on motoneurons themselves, because we found that their direct activation with clonidine hyperpolarizes the motoneurons. Indeed, previous studies have shown that ␣ 2 receptors on motoneurons induce a hyperpolarization by blocking I h currents (Adachi et al 2005;Parkis and Berger 1997;Rekling et al 2000), and such I h currents contribute ϩ10 mV to the resting potential in our chronic spinal rats ). Furthermore, ␣ 2 receptor expression can be detected throughout the spinal cord with the highest densities in the superficial dorsal horn and moderate densities in the portion of be ventral horn containing motoneurons (Giroux et al 1999;Roudet et al 1994).…”

“…NA and other monoamines increase motoneuron excitability (Adachi et al 2005;Elliott and Wallis 1992;Funk et al 1994;Li et al 2004b;Rekling et al 2000) by facilitating persistent inward currents (PICs), consisting of low-voltage activated calcium (Ca PIC) and sodium (Na PIC) currents (Harvey et al 2006b,c;Lee and Heckman 1999). These monoamine-dependent PICs are essential for motoneuron function, amplifying synaptic inputs to motoneurons and providing the basic capacity for sustained depolarization and firing (Harvey et al 2006b;Hounsgaard et al 1988;Lee and Heckman 2000).…”

Chronic Intermittent Hypoxia Alters Density of Aminergic Terminals and Receptors in the Hypoglossal Motor Nucleus

“…5-HT may enhance activity of XII motoneurons by its presynaptic inhibitory action on transmission of glycinergic inhibition (53), and it may reduce XII motoneuronal activity by its presynaptic inhibitory action on transmission of glutamatergic inputs (54), with both mediated by 5-HT 1B receptors. Inhibitory effects mediated by a 2 -adrenoceptors have also been described, but their underlying mechanisms need further studies (55,56). Thus, although we emphasize the postsynaptic excitatory effects because they are best documented in vivo and appear to be most powerful, the net functional effects of the anatomical changes described in our study may be more complex.…”

α2-Adrenergic blockade rescues hypoglossal motor defense against obstructive sleep apnea

“…Of note, previous studies have shown that HMs may be subject to an α 2C -adrenoceptor (but not α 2A -adrenoceptor) subtype-mediated inhibition (47,48). However, subsequent studies revealed that this effect is prominent only in neonatal animals (49) and does not involve pre-or postsynaptic inhibition of glutamatergic transmission (50). Thus, the mechanism of action of yohimbine therapy in adult animals probably does not involve the modulation of glutamate transmission of inspiratory drive to HMs through blockade of pre-or postsynaptic α 2C -adrenoceptor subtype.…”