Rescue of excitation by inositol following Li⁺-induced block in Limulus ventral photoreceptors

Abstract

The phosphoinositide (PI) intracellular signaling pathway, which triggers Ca2+ release from intracellular stores, appears to be a central feature of phototransduction in most invertebrate species studied. Procedures designed to inhibit PI-pathway reactions cause suppression of excitation to dim lights. However, in Limulus photoreceptors, responses to bright stimuli are in fact enhanced by some of these procedures, suggesting that PI metabolism is not obligatory for light-induced excitation. Other studies, however, suggest that Ca2+ release is obligatory for excitation. We studied this issue by examining the effects of PI-pathway inhibitor, Li+, on electrophysiological responses to light in Limulus photoreceptors. Li+ is reported to cause depletion of intracellular PI-pathway intermediate, inositol; and it offers the pharmacological advantage that its block can be bypassed by introducing exogenous inositol. Introduction of Li+ caused a very slowly developing but complete suppression of responses to dim stimuli. In contrast, Li+ caused a rapidly developing but partial suppression of responses to bright stimuli. Li(+)-induced suppression was reversed by exogenous introduction of inositol. In addition, inositol prevented Li(+)-induced suppression of excitation. Li+ enhanced light adaptation (light-induced desensitization) but slowed response deactivation, indicating a difference in the processes underlying these phenomena. Li+ slowed dark adaptation, the recovery of sensitivity following light adaptation. All of these effects were prevented or rescued by extracellularly applied inositol, suggesting the presence of a transmembrane inositol transport system. The overall results suggest that PI-dependent signaling is central and obligatory for excitation in Limulus, at least for responses to dim to moderate illumination. The failure of Li+ to suppress bright light-induced excitation completely may be due to a failure of Li+ to block PI metabolism completely, as in other systems; however, it may point to a parallel, PI-independent excitation pathway possessing very low light sensitivity when PI metabolism is inhibited.

Sodium/myo-inositol cotransporter 1 and myo-inositol are essential for osteogenesis and bone formation

“…Most studies of MI have focused on the neural and renal systems, the sites of high concentrations of MI 4, 5. MI has been shown to be an effective treatment for several psychiatric disorders, such as panic disorder, obsessive‐compulsive disorder, and depression,6–8 and to be useful in the management of the side effects of lithium therapy and in cancer prevention 9, 10. Previous studies also have proven that derivatives and the related pathways of MI are involved in bone metabolism.…”

Timing of Ca2+ Release from Intracellular Stores and the Electrical Response of Limulus Ventral Photoreceptors to Dim Flashes

“…Rapid release of Ca 2 ϩ by flash photolysis of intracellular caged InsP 3 or caged Ca 2 ϩ activates this conductance within a few milliseconds (Ukhanov and Payne, 1997). Pharmacological blockade of light-induced Ca 2 ϩ release greatly diminishes the electrical response to dim or moderately intense light flashes and slows the onset of the electrical response at all intensities Frank and Fein, 1991;Shin et al, 1993;Nagy and Contzen, 1997;Johnson et al, 1998). Cyclopiazonic acid 736 Timing of Ca 2 ϩ Release in Limulus Photoreceptors (CPA), an agent that depletes intracellular Ca 2 ϩ stores (Mason et al, 1991), eliminates the highly amplified response to single quanta (Dorlöchter et al, 1999).…”