Distinguishing between roles for calcium in Limulus photoreceptor excitation

The role for Ca2+ in the excitation process by which light opens membrane channels in Limulus photoreceptors is discussed. Light initiates a phospholipase C/IP3 pathway that results in a rapid elevation of intracellular Ca2+, but whether this elevation is causal in triggering the light response or merely synergistic to some other second messenger pathway has been unclear. We have developed a procedure using progressive injection of Ca2+ buffers that distinguishes between mediation and synergy models [Shin J-H. Richard EA. Lisman JE. (1992) Ca2+ is an obligatory intermediate in the excitation cascade of Limulus photoreceptors. Neuron, 11, 845-855]. Our conclusion is that Ca2+ mediates all phases of the light-response. Models of this kind had previously been rejected because intracellular injection of Ca2+ buffer can lead to an increase of the late component (> 200 ms) of the response to bright, sustained light. We have used computer simulations of IP3 mediated Ca2+ release to show that the positive and negative regulation of this process by Ca2+ itself together with other feedback loops can explain counterintuitive effects of Ca2+ buffers.