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A patch-clamp study of voltage-gated ion channels in neurones of the rat ventral cochlear nucleus.

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thesis
posted on 2015-11-19, 08:44 authored by Joanne Marie. Doughty
The bushy cells of anteroventral cochlear nucleus (aVCN), in the auditory brainstem, project to the principal neurones of the contralateral medial nucleus of the trapezoid body via a giant glutamatergic synapse - the calyx of Held. There is evidence of presynaptic modulation of transmission at this synapse by metabotropic glutamate receptors (mGluRs). This thesis examines voltage-gated potassium and calcium currents in the bushy cell bodies which give rise to the calyx of Held, to ascertain if they are the target of presynaptic modulation by mGluRs. Three different neuronal preparations from the VCN of neonatal Lister Hooded rats were used - primary cultures, acutely isolated cells and brain slices. Whole cell patch-clamp measurements were made of somatic voltage-gated currents. The effects of mGluR agonists on these currents were tested. At least three kinetically and pharmacologically distinct potassium currents could be characterised, but there was no evidence that these currents were modulated by mOluRs. Calcium currents could be measured that were consistent with high-voltage activated (HVA) and low-voltage-activated (LVA) calcium currents described for other cell preparations. The HVA currents could be dissected using dihydropyridines (DHPs) and omega-conotoxin. A somatic, DHP-sensitive HVA calcium current was shown to be depressed by mGluR agonists, while DHP-insensitive HVA currents, and LVA currents were unaffected. Demonstration of the depression of a somatic L-type calcium current in the bushy cells of the aVCN did not provide a model for a mechanism of presynaptic depression of transmission at the calyx of Held. The physiological function of this effect is more likely to be a post-synaptic mechanism which may limit the risk of excitotoxicity in the bushy cell during high frequency stimulation of its glutamatergic synaptic input.

History

Date of award

1996-01-01

Author affiliation

Cell Physiology and Pharmacology

Awarding institution

University of Leicester

Qualification level

  • Doctoral

Qualification name

  • PhD

Language

en

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