A direct signaling role for phosphatidylinositol 4,5-bisphosphate (PIP2) in the visual excitation process of microvillar receptors

In microvillar photoreceptors the pivotal role of phospholipase C in light transduction is undisputed, but previous attempts to account for the photoresponse solely in terms of downstream products of phosphatidylinositol 4,5-bisphosphate (PIP2) hydrolysis have proved wanting. In other systems PIP2 has been shown to possess signaling functions of its own, rather than simply serving as a precursor molecule. Because illumination of microvillar photoreceptors cells leads to PIP2 breakdown, a potential role for this phospholipid in phototransduction would be to help maintain some element(s) of the transduction cascade in the inactive state. We tested the effect of intracellular dialysis of PIP2 on voltage-clamped molluscan photoreceptors and found a marked reduction in the amplitude of the photocurrent; by contrast, depolarization-activated calcium and potassium currents were unaffected, thus supporting the notion of a specific effect on light signaling. In the dark, PIP2 caused a gradual outward shift of the holding current; this change was due to a decrease in membrane conductance and may reflect the suppression of basal openings of the light-sensitive conductance. The consequences of depleting PIP2 were examined in patches of light-sensitive microvillar membrane screened for the exclusive presence of light-activated ion channels. After excision, superfusion with anti-PIP2 antibodies induced the appearance of single-channel currents. Replenishment of PIP2 by exogenous application reverted the effect. These data support the notion that PIP2, in addition to being the source of inositol trisphosphate and diacylglycerol, two messengers of visual excitation, may also participate in a direct fashion in the control of the light-sensitive conductance.