L-Glutamate inhibits the K+ conductance that dominates the electrical
behavior of a Muller glial cell. The effect of glutamate is enhanced b
y simultaneous exposure to dopamine. L-Glutamate acts at a metabotropi
c receptor that controls the K+ conductance through two pathways. A ra
pid pathway produces a partial inhibition in less than 2 s. Thereafter
, a slow pathway progressively inhibits the conductance with a half-ti
me of minutes. Pathways initiated by L-glutamate and dopamine appear t
o converge on and stimulate adenylyl cyclase. A subsequent step is the
activation of a cAMP-dependent protein kinase, PKA. The local overflo
w of L-glutamate from active synapses may functionally remove K+ chann
els from nearby glial membranes. A uniform rise in extracellular L-glu
tamate concentration, as might occur during pathological conditions, s
hould suppress a glial cell's K+ conductance and allow other voltage-d
ependent processes to be influenced by depolarization.