Our studies of
potassium channels aim at learning about the function of
these channels both at the level of the protein and at the
level of the physiological contribution of these proteins
to the control of excitability and signaling in the nervous
system.
At the moment
one focus of our studies is the way neurotransmitter actions
are mediated via modulation of inwardly rectifying potassium
channels. We have shown that GIRK channels are directly
activated by Gbg
subunits, so
as to mediate the effect of inhibitory transmitters such
as acetylcholine in the heart and GABA in the brain. At
the level of the channel protein we are pursuing questions
concerning the mechanism of G protein gating. At the level
of the mammalian central nervous system we hope to define
the molecular composition of the channels that are effectors
of various transmitter receptors in various neurons. A more
challenging question concerns how only a subset of G protein
coupled receptors of a neuron activate these channels as
Gßg effectors. In contrast to inhibitory transmitters
which can activate GIRK channels, some of the excitatory
transmitters activate Gq/11 coupled receptors and suppress
inwardly rectifying potassium channel activities. The mechanism
for this modulation is under investigation.
