Several lines of evidence suggest a physiological role for Cu2+ in reg
ulating nervous system function. In the present study using whole-cell
patch-clamp recording, Cu2+ greatly enhanced current activated by 10
mu M ATP in the majority of rat nodose ganglion neurons. The enhanceme
nt was concentration-dependent between 1 and 50 mu M Cu2+, and had an
EC(50) of 6.1 mu M. Cu2+ shifted the ATP concentration-response curve
to the left in a parallel manner. However, Cu2+ did not enhance ATP-ac
tivated current in the presence of a maximally-effective concentration
of Zn2+. The observations suggest that Cu2+ increases the affinity of
the receptor for ATP by acting at the Zn2+ modulatory site. In additi
on, a subset of neurons in the nodose ganglion express ATP-gated recep
tor-channels that are insensitive to modulation by physiological conce
ntrations of Cu2+, Zn2+ and protons.