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Title: Modulation of membrane excitability and ion channels by intracellular Ca⁺² and neurotransmitters in hippocampal neurons
Author: Tedoldi, A.
ISNI:       0000 0004 7659 8299
Awarding Body: UCL (University College London)
Current Institution: University College London (University of London)
Date of Award: 2015
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The modulation of ion channels and neuronal excitability by Ca⁺² and neurotransmitters (GABA and 5-HT) was investigated with whole-cell patch clamping recordings in acute hippocampal slices. The first part of the project aimed to study the role of ryanodine type-3 receptors (RyR3) in the generation and maintenance of the slow afterhyperpolarising current (sIAHP). sIAHP potentiates in response to repetitive stimulation and the consequent increase of intracellular Ca⁺² concentration. RyR3 knock-out mice showed a faster potentiation of the current than wild-type littermates. Once the current was stable, however, application of ryanodine reduced the sIAHP in both knock-out and control mice. Thus, RyR3 seems to play a role in the early modulation of the current, possibly by affecting the balance of Ca⁺² sources that activate the sIAHP, but it is not necessary for the maintenance of the sIAHP. In the second part of my PhD, I studied the effects of the GABAB receptor agonist baclofen and 5-HT on membrane excitability in hippocampal neurons. Application of either baclofen or 5-HT activated an outward current that had 3 different components. The first component (~50% of total current) was blocked by tertiapin-Q or Cs⁺, indicating the involvement of GIRK channels. The second component (~40%) was inhibited by bupivacaine and fully blocked by Ba⁺², suggesting a role for members of the K2P family in mediating this current. The third component (~10%) was mainly visible when all the K⁺ components of the outward current had been blocked and had features consistent with a Cl⁻ current. Based on our results, activation of GABAB and 5-HT1A receptors elicits a chloride current as well as two types of K⁺ currents to decrease the membrane excitability of hippocampal neurons.
Supervisor: Pedarzani, P. Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available