Potassium channel and Calcium signalling in Drosophila learning

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• James Hodge, Department of Physiology and Pharmacology, University of Bristol
• Thursday 07 October 2010, 16:00-17:00
• Part II Lecture Theatre, Department of Zoology.

If you have a question about this talk, please contact Irene Miguel-Aliaga.

Kv7 voltage-gated potassium channels are encoded by the KCNQ gene family and serve a range of important physiological functions. This is highlighted by the fact that four of the five members of the KCNQ family are related to different hereditary diseases. This has made KCNQ family an important pharmacological target for treating disease characterized by changes in membrane excitability. Drosophila contains only one KCNQ channel, dKCNQ. We have compared the electrophysiology and pharmacological properties of dKCNQ to the mammalian KCNQ channels, and find that dKCNQ encodes an M-current. We find that many of the clinically relevant KCNQ modulators are also effective on dKCNQ. In addition we demonstrate that both KCNQ2 /3 and dKCNQ are highly sensitive to block by ethanol and the potential cognitive enhancers, linopridine and XE991 . In vivo dKCNQ is most highly expressed in the nervous system and as has been reported in the heart (where mutants display cardiac arrhythmias), dKCNQ expression decreases with age. We find that dKCNQ mutants display (age-dependent) learning deficits in the olfactory-shock assay and an ethanol sensitivity phenotype. We are also using Drosophila to study the neuronal mechanism by which CASK and CaMKII mutants lead to learning defects. CASK is a PDZ containing MAGUK scaffolding protein, mutations of which cause FG syndrome, microcephaly, X-linked mental retardation and X-linked brain malformation. We find Drosophila CASK associates with CaMKII negatively regulating the ability of synaptic CaMKII to autophosphorylate at T287 thereby becoming calcium-independent and constitutively active (the “molecular memory” switch) resulting in disruption of different phases of Drosophila learning and memory.

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