The relatively sparse vasculature of the retina minimizes
obstruction to incoming light, but also poses a challenge to
fulfilling the metabolic demands of retinal neurons. An efficient
process for distributing energy supplies to areas of need is
likely to involve neuron-derived vasoactive signals. However,
knowledge of the mechanisms by which capillary perfusion is
regulated by neuron-to-vascular signaling is limited. Potential
targets of vasoactive molecules released from nerve cells are
the pericytes, which are positioned on the endothelial walls
of microvessels and are thought to play a role in controlling
the microcirculation. In this study, we assessed the effect
of dopamine on pericyte physiology. Because dopaminergic neurites
are closely associated with microvessels that express dopamine
receptors, this molecule is a putative neuron-to-capillary signal,
as well as neurotransmitter. We used the perforated-patch
configuration of the patch-clamp technique to monitor the
whole-cell currents of pericytes located on microvessels freshly
isolated from the adult rat retina. In 43% (58/134) of the sampled
pericytes, we found that dopamine reversibly activated a
hyperpolarizing current, which increased the membrane potential
by 19 ± 1 mV. This dopamine-induced current was inhibited
by the ATP-sensitive potassium (KATP) channel blocker,
glibenclamide. Consistent with a signaling pathway involving
D1 dopamine receptors, adenylate cyclase and protein
kinase A (PKA), the selective D1 antagonist, SCH23390,
inhibited the hyperpolarizing effect of dopamine; the activator
of adenylate cyclase, forskolin, mimicked the dopaminergic effect,
and H89, which inhibits PKA, significantly reduced the
hyperpolarization induced by dopamine. Taken together, our
experiments indicate that a mechanism involving D1
dopamine receptors, adenylate cyclase, and PKA activates
KATP currents in retinal pericytes. Our observations
support the hypothesis that, in addition to being a neuromodulator,
dopamine also serves as a signal linking neuronal activity with
the function of the pericyte-containing microvasculature.