Modulation of respiratory activity of neonatal rat phrenic motoneurones by serotonin.

Abstract

SUMMARY1. The effects of serotonin on phrenic motoneurones were studied in an in vitro preparation of the isolated brainstem and spinal cord from neonatal rats.2. Serotonin (5-HT; ) 5-10 ltM) increased inspiratory-modulated phrenic nerve activity and produced a small amount of tonic activity during expiration. Inspiratory-modulated activity of the fourth cervical ventral root also increased, but was accompanied by robust tonic activity, which often obscured the rhythmic activity.3. Serotonin, in both normal and tetrodotoxin-containing medium, depolarized phrenic motoneurones and increased cell input resistance. Serotonin also increased inspiratory-modulated firing as well as the response of phrenic motoneurones to injected current. The y-intercept of the relationship between firing frequency and injected current (f-I) was increased, but the slope was not affected. There was no bistable firing behaviour.4. Under voltage clamp conditions, 5-HT produced a tonic inward current of 0-07-037 nA. This current increased with less negative holding potentials and decreased with more negative holding potentials (-75 to -90 mV) but did not reverse.5. In addition, 5-HT decreased inspiratory-modulated synaptic current by 23 + 6 %. The degree of attenuation was not affected by holding potential. The time course of the decrease in inspiratory-modulated synaptic current was similar to the changes seen in tonic inward current and input resistance.6. Depolarization, tonic inward current, and shift in the f-I relationship produced by 5-HT were antagonized by the 5-HT211c receptor antagonist ketanserin and mimicked by the 5-HT2/1l agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane HCI (DOI). However, the 5-HIT induced decrease in inspiratory-modulated synaptic current was not reduced by ketanserin nor mimicked by DOI. 7. We conclude that exogenously applied 5-HT simultaneously increases cell excitability and decreases inspiratory-modulated synaptic current in phrenic motoneurones via different types of receptors. When these responses occurred simultaneously, the increase in excitability predominated and the net effect was an augmentation of inspiratory-modulated phrenic motoneurone activity.

Endogenous Activation of Serotonin-2A Receptors Is Required for Respiratory Rhythm GenerationIn Vitro

“…Consistent with our findings, PKC modulates transient (Astman et al, 1998;Sitges et al, 1998;Schreibmayer, 1999) and persistent sodium currents (Astman et al, 1998;Franceschetti et al, 2000), and it has been proposed that these effects on sodium currents increase the neuronal excitability (Astman et al, 1998;Franceschetti et al, 2000). The activation of 5-HT 2A receptors has been associated with the induction of a tonic inward current (Lindsay and Feldman, 1993) that is Na ϩ dependent (Lee et al, 1999). In this study, we show that the inhibition of endogenous activation of 5-HT 2A receptors decreases the persistent and transient sodium current in the re- (COCKTAIL; top trace), the pacemaker neuron continues to generate intrinsically rhythmic activity (bottom trace).…”

“…Activation of 5-HT 2A receptors has a well documented excitatory effect not only in the respiratory network but also on different areas in the CNS (Araneda and Andrade, 1991;Lindsay and Feldman, 1993;Marek and Aghajanian, 1996). At the cellular level, ionophoresis of 5-HT 2A agonists (␣-Me-5-HT and DOI) depolarizes membrane potential and increases action potential frequency in respiratory neurons (Lalley et al, 1995;Onimaru et al, 1998), which results in an increase in respiratory rhythmic activity in the brainstem slice preparation (Al-Zubaidy et al, 1996;Onimaru et al, 1998).…”

Modulation of inspiratory drive to phrenic motoneurons by presynaptic adenosine A1 receptors

“…Neurons subjected to experimental measurements and data analysis satisfied criteria previously described (Liu et al, 1990;Lindsay and Feldman, 1993). Briefly, these neurons had resting membrane potentials of at least -60 mV and displayed rhythmic synaptic drive currents in synchrony with the inspiratory burst activity on the C, ventral root.…”

Long‐term facilitation of inspiratory intercostal nerve activity following carotid sinus nerve stimulation in cats.

“…Furthermore, localized injections of serotonin or serotonin agonists elicit both facilitatory and inhibitory influences on important classifications of medullary respiratory neurones (Sessle & Henry, 1985;Arita & Ochiishi, 1991). However, the net influence of increased supraspinal serotonin is an increase in respiratory frequency rather than nerve burst amplitude (Monteau, Morin, Hennequin & Hilaire, 1990;Morin, Monteau & Hilaire, 1991;Lindsay & Feldman, 1993). Millhorn et al (1980a) suggested that LTF operates via supraspinal mechanisms, a theory based on the observation that LTF occurs via changes in both phrenic burst amplitude and frequency.…”