Leaney, Joanne Louise; (1997) A comparative study of three different chloride currents in rat sympathetic neurones. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Cl- ions are the most abundant anion in cells. Cl- conducting channels have been proposed to be involved in several cellular processes. These include the modulation of electrical excitability and synaptic inhibition, the regulation of intracellular pH and the regulation of cell volume. In this thesis three types of Cl- channels in rat superior cervical ganglion neurones have been investigated. These are a Ca2+ and protein kinase C-dependent Cl- current (ICl(m)), a hyperpolarization-activated Cl- current (ICL(HP)) and a swelling-activated Cl- current (Icl(swell))- These three currents differ in several properties including biophysical characteristics, sensitivity to pharmacological agents, anion permeability, Ca2+-dependence and involvement of second messenger pathways. Icl(m) is induced synergistically by Ca2+ and diacylglycerol. Consequently it can be activated by the actions of the excitatory neurotransmitter, acetylcholine, which causes a rise in intracellular Ca2+ via the activation of Ca2+ -permeable nicotinic ionotropic receptors, and generates diacylglycerol by stimulating muscarinic receptors. The hyperpolarization-activated Cl- current, (ICL(HP)), shows strong voltage- and time-dependence, is Ca2+-independent and is sensitive to block by the divalent cations, Cd2+ and Zn2+. Icl(swell) is activated in response to hypotonicity-induced cell swelling. The movement of Cl- ions out of the cell is accompanied by water which thus leads to a reversal of cell swelling (Regulatory Volume Decrease mechanism). I have shown that Icl(swell) is different to previously identified Cl- currents in these cells but shares several properties with swelling-activated Cl- currents in other cell types. To conclude, I have studied three types of neuronal Cl- currents which are distinct from one another. Icl(m) and ICL(HP) may have a physiological role in the regulation of electrical excitability, and Icl(swell) in the response of cells to osmolarity changes under both physiological and pathological conditions.

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