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Title: The electrophysiology of adult rat facial motoneurones in a novel in vitro brainstem slice : ionic mechanism and pharmacological characterisation of serotonin (5-hydroxytryptamine)-evoked depolarisation
Author: Larkman, P. M.
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1990
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This study describes intracellular recordings from adult rat cranial motoneurones constituting the Facial Motor Nucleus of the brainstem, using a novel in vitro slice. Facial motoneurones (FMn's) were identified histologically using retrograde labelling with HRP and by antidromic invasion. Antidromically evoked action potentials were overshooting, with initial segment and somato-dendritic components and were often followed by depolarizing potentials. Directly-evoked overshooting action potentials were followed by a fast after hyperpolarization, a brief delayed depolarization and a longer lasting apamin sensitive ahp which was annulled near the predicted equilibrium potential for K+ ions. Intracellular Cs+ led to a widening of the spike and a reduction in the amplitude of the ahp. Depolarizing current pulses of longer duration showed a depolarizing pre-potential to precede spike generation. Passive membrane properties were investigated using longer duration current pulses and showed the response to be ohmic over a narrow voltage range around rest. The time constant for membrane charging (T) ranged from 1.5 to 4msec. Larger hyperpolarizing current pulses evoked voltage responses with a time dependent sg characteristic of inward 'anomalous' rectification which reached steady state within the pulse. A rebound depolarizing potential occurred subsequent to the current pulse. Voltage clamp studies showed this sag to be the result of a slowly developing inward current. Intracellular recordings in vi;ro from a variety of central ncuronal types have shown both inhibition and excitation to be modulatory consequences of serotonin receptor activation. lontophoretic application of 5-HT in vivo on rat facial motoneurones has been shown to evoke a depolarization associated with increased input resistance (Rm). This study has confirmed and further investigated the mechanism and pharmacology of this action in vitro. Supcrfusion of 5-HT evokes a slow depolarization associated with increased Rm, and a lengthening of T through a direct action on the post-synaptic membrane. Manual clamping of the membrane potential at the peak of the 5-HT response back dependent rectification. Estimated reversal potentials from peak current-voltage plots under these conditions were more negative than the predicted K^ equilibrium potential. Increasing the extracellular K+ concentration, [K+]0, shifted the reversal potential to more positive values in a manner predicted by the Ncrnst equation for a K+ conductance. Nor-adrenaline (NA) evoked a similar depolarization associated with increased Rm. However, lower NA concentrations were needed for equivalent size depolarizations and the change in input resistance was usually greater. The estimated reversal potential for the NA effect was more positive than for 5-HT and when manually clamped agreed well with the predicted value. Increased [K+]0 changed the reversal potential to a more positive level. Voltage clamp studies show both 5-HT and NA to evoke a slow inward current associated with a decrease in conductance which was greater for NA. 8-OH-DPAT and dipropyl-5-CT, 5-HTjx selective agonists and 2-CH3-5-HT a 5-HTs agonist were unable to mimic or antagonise 5-HT evoked responses. Methysergide selectively antagonized the 5-HT response leaving the NA response unaffected. LY-53857 also antagonised the 5-HT response while kctanserin was unable to fully abolish 5-HT depolarization even after prolonged exposure. Spiperone, methiothepin and ICS 205-930 were all ineffective antagonists.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available