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Title: 5-hydroxytryptamine modulation of calcium currents recorded from mammalian central serotonergic neurones
Author: McAllister-Williams, R. H.
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1993
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It has previously been shown that 5-hydroxytryptamine (5-HT; serotonin), is able to inhibit high threshold voltage dependent (HVA) calcium currents in 5-HT containing dorsal raphé(DR) neurones via 5-HT1A receptors (Penington & Kelly, 1990, Neuron, 4,751). This inhibition involves a retardation of current activation, and a partial reduction in amplitude. These calcium currents, and the action of 5-HT, have been further characterised using the whole cell patch clamp method in acutely isolated adult rate DR cells. The effect of temperature on HVA currents has been studied in considerable detail. Results of the temperature dependency are in keeping with the presumed heterogeneous nature of HVA current in neuronal cells. In addition, it was found that a fast inactivating component is uncovered by increases in temperature to 25oC or above, and this component is voltage sensitive, decreasing in prominence with increasing sizes of test pulses. This is in keeping with at least three HVA components. While the temperature coefficient (Q10) of current amplitude and inactivation rate was found to be in the expected 2-3 range, the activation rate was discovered to be much more sensitive, being between 10 and 12. Stimulation of 5-HT1A receptors, or direct G-protein activation had no effect on HVA calcium current amplitude Q10's, but led to a dramatic reduction in the activation rate Q10 down to 2-3. This could be reversed by the prior application of large depolarising prepulses prior to the test pulse. The possible involvement of phosphorylation in the maintenance of HVA calcium currents and the action of 5-HT was investigated using phosphatase inhibitors. It was found that phosphatase inhibition tended to lead to a gradual increase in current amplitude over a period of some minutes, but then had no clear effect on the subsequent rate of time dependent decrease in current amplitude ('rundown'). With the single dose of inhibitor used, it was found that 5-HT1A receptor stimulation, while still causing some reduction in current amplitude, was unable to lead to a reduction in activation rate Q10.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available