anthelmintics ivermectin Flashcards
what does ivermectin do
potent and persistant paralysis of nematode pharyngeal and body wall muscle
what channel does it have the highest affinity for
glutamate gated chloride channels
what did we expression clone from c.elegans
Glucl (alpha)
GluCl (beta) subuntis
how did we express them in the xenopus oocyte
either single or together
what did the alpha and Beta subunits show
gluCl alpha responds to ivermectin
Glucl beta responds to glutamate
what does coexpression of alpha and beta do
responds to glutamate
is +vely allosterically modulated by nM ivermectin
4 c.elegan genes encoding GluCL alpha
2 are alternitively spliced
A 1 = glc-1
A 2a/b = avr-15
A 3a/b = avr-14
A 4 = glc-3
what codes for GluCL b
glc-2
c.elegan
what do the pharyngeal muscles express
avr-15
glc-2
mutants of avr-15 what happens
does not respond to ivermectin
indicating involvement of GluCL (alpha)2
even thought the pharyngeal muscles are not inhibited by ivermectin in mutants
population of avr-15 mutants exposed to ivermectin are still paralysed
thus GluCl channels in the pharynx are not required for paralytic effects
GluCl channel regulated forward movement
where is it conserved between c.elegans
avr-14
gluCl alpha 3
what is most likely to be the parasitic action of GluCl alpha 3
potent activation of GluCl in motornervous system in nematodes
precise role yet to be discovered
resistance via c.elegans
requires mutation of at least 3 genes
glc-1
avr-14
and avr-15
further genes for resistance
regulating membrane permiability (osm-1)
