Tedoldi, A;
(2015)
Modulation of membrane excitability and ion channels by intracellular Ca⁺² and neurotransmitters in hippocampal neurons.
Doctoral thesis , UCL (University College London).
Abstract
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.
| Type: | Thesis (Doctoral) |
|---|---|
| Title: | Modulation of membrane excitability and ion channels by intracellular Ca⁺² and neurotransmitters in hippocampal neurons. |
| Language: | English |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Neuro, Physiology and Pharmacology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1472398 |
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