title: Depletion of calcium stores regulates calcium influx and signal transmission in rod photoreceptors.
abstract: 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 [Ca(2+)](i) in rod inner segments and synaptic terminals. Sustained Ca(2+) entry into rod cytosol is augmented by store depletion, blocked by La(3+) and Gd(3+) and suppressed by organic antagonists MRS-1845 and SKF-96365. Store depletion and the subsequent Ca(2+) 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 Ca(2+) entry. Silencing of TRPC1 expression with small interference RNA disrupted SOCE in rods, but had no effect on cone Ca(2+) signalling. Rods were immunopositive for TRPC1 whereas cone inner segments immunostained with TRPC6 channel antibodies. Thus, SOCE modulates Ca(2+) homeostasis and light-evoked neurotransmission at the rod photoreceptor synapse mediated by TRPC1.
authors.affiliation: Department of Ophthalmology, UCSF School of Medicine, San Francisco, CA 94143, USA.
authors.forename: Tamas
authors.initials: T
authors.lastname: Szikra
authors.forename: Karen
authors.initials: K
authors.lastname: Cusato
authors.forename: Wallace B
authors.initials: WB
authors.lastname: Thoreson
authors.forename: Peter
authors.initials: P
authors.lastname: Barabas
authors.forename: Theodore M
authors.initials: TM
authors.lastname: Bartoletti
authors.forename: David
authors.initials: D
authors.lastname: Krizaj