Depletion of calcium stores regulates calcium influx and signal transmission in rod photoreceptors

Tonic synapses are specialized for sustained calcium entry and transmitter release, allowing them to operate in a graded fashion over a wide dynamic range. We identified a novel plasma membrane calcium entry mechanism that extends the range of rod photoreceptor signalling into light-adapted conditions. The mechanism, which shares molecular and physiological characteristics with store-operated calcium entry (SOCE), is required to maintain baseline [Ca²⁺]_i in rod inner segments and synaptic terminals. Sustained Ca²⁺ entry into rod cytosol is augmented by store depletion, blocked by La³⁺ and Gd³⁺ and suppressed by organic antagonists MRS-1845 and SKF-96365. Store depletion and the subsequent Ca²⁺ influx directly stimulated exocytosis in terminals of light-adapted rods loaded with the activity-dependent dye FM1-43. Moreover, SOCE blockers suppressed rod-mediated synaptic inputs to horizontal cells without affecting presynaptic voltage-operated Ca²⁺ entry. Silencing of TRPC1 expression with small interference RNA disrupted SOCE in rods, but had no effect on cone Ca²⁺ signalling. Rods were immunopositive for TRPC1 whereas cone inner segments immunostained with TRPC6 channel antibodies. Thus, SOCE modulates Ca²⁺ homeostasis and light-evoked neurotransmission at the rod photoreceptor synapse mediated by TRPC1.