Ascorbic acid (AA), a neuromodulator in the vertebrate
CNS, is released from glutamatergic neurons in exchange
with glutamate uptake and, in turn, modulates the release
of both glutamate and dopamine. We have reported that voltage-gated
K+ currents (IK(V))
in ON-mixed rod/cone bipolar cells (Mb) were suppressed
60% by 100–200 μM AA when added to an ascorbate-free
solution. However, as the in vivo [AA]o
in retina is about 200 μM, we studied the effects of changes in [AA]o on IK(V)
when [AA]o was varied around a baseline concentration
of 200 μM. Whole-cell currents were recorded with patch-clamp methods
from goldfish Mb cells in retinal slices, bathed in a solution
containing 200 μM AA. We found that (1)
IK(V) was enhanced (180 ±
36%, n = 9) by increases of [AA]o
less than 40 μM with an average latency of 8 min. (2)
However, IK(V) was
suppressed without an appreciable latent period by two
conditions: increases more than 40 μM [AA]o
and decreases by any amount greater than 10 μM. (3)
Effects of Δ[AA]o on
IK(V) were blocked by a D1 dopamine
receptor antagonist, SCH 23390, but not by a D2 receptor
antagonist, spiperone. Increased concentrations of a D1
agonist (SKF 38390) and dopamine had similar concentration-dependent
effects on IK(V) as
did AA, even in the presence of 200 μM ascorbate.
Ascorbate has complicated concentration-dependent effects
on IK(V) of Mb cells
in vitro that were mediated by D1 dopamine receptors,
suggesting that dopamine and ascorbate may be involved
reciprocally in modulating IK(V),
with consequences on the transmission of rod signals to
the inner retina.
Non-steady-state measurement of in vivo receptor binding with positron emission tomography: "dose-response" analysis
