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SUMMARY:Potassium channel and Calcium signalling in Drosophila learning - 
 James Hodge\, Department of Physiology and Pharmacology\, University of Br
 istol
DTSTART:20101007T150000Z
DTEND:20101007T160000Z
UID:TALK26740@talks.cam.ac.uk
CONTACT:Irene Miguel-Aliaga
DESCRIPTION:Kv7 voltage-gated potassium channels are encoded by the KCNQ g
 ene 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 ch
 anges in membrane excitability. Drosophila contains only one KCNQ channel\
 , dKCNQ. We have compared the electrophysiology and pharmacological proper
 ties of dKCNQ to the mammalian KCNQ channels\, and find that dKCNQ encodes
  an M-current. We find that many of the clinically relevant KCNQ modulator
 s 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 cog
 nitive enhancers\, linopridine and XE991. In vivo dKCNQ is most highly exp
 ressed 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.\nWe are al
 so using Drosophila to study the neuronal mechanism by which CASK and CaMK
 II mutants lead to learning defects. CASK is a PDZ containing MAGUK scaffo
 lding protein\, mutations of which cause FG syndrome\, microcephaly\, X-li
 nked mental retardation and X-linked brain malformation. We find Drosophil
 a CASK associates with CaMKII negatively regulating the ability of synapti
 c CaMKII to autophosphorylate at T287 thereby becoming calcium-independent
  and constitutively active (the “molecular memory” switch) resulting i
 n disruption of different phases of Drosophila learning and memory.\n
LOCATION:Part II Lecture Theatre\, Department of Zoology
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