cAMP/PKA-dependent increases in Ca Sparks, oscillations and SR Ca stores in retinal arteriolar myocytes after exposure to vasopressin.

O. Jeffries, Mary McGahon, Peter Bankhead, M.M. Lozano, Norman Scholfield, Timothy Curtis, Graham McGeown

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)

Abstract

PURPOSE: To investigate the effects of arginine vasopressin (AVP) on Ca(2+) sparks and oscillations and on sarcoplasmic reticulum (SR) Ca(2+) content in retinal arteriolar myocytes. METHODS: Fluo-4-loaded smooth muscle in intact segments of freshly isolated porcine retinal arteriole was imaged by confocal laser microscopy. SR Ca(2+) store content was assessed by recording caffeine-induced Ca(2+) transients with microfluorimetry and fura-2. RESULTS: The frequencies of Ca(2+) sparks and oscillations were increased both during exposure to, and 10 minutes after washout of AVP (10 nM). Caffeine transients were increased in amplitude 10 and 90 minutes after a 3-minute application of AVP. Both AVP-induced Ca(2+) transients and the enhancement of caffeine responses after AVP washout were inhibited by SR 49059, a V(1a) receptor blocker. Forskolin, an activator of adenylyl cyclase, also persistently enhanced caffeine transients. Rp-8-HA-cAMPS, a membrane-permeant PKA inhibitor, prevented enhancement of caffeine transients by both AVP and forskolin. Forskolin, but not AVP, produced a reversible, Rp-8-HA-cAMPS insensitive reduction in basal [Ca(2+)](i). CONCLUSIONS: AVP activates a cAMP/PKA-dependent pathway via V(1a) receptors in retinal arteriolar smooth muscle. This effect persistently increases SR Ca(2+) loading, upregulating Ca(2+) sparks and oscillations, and may favor prolonged agonist activity despite receptor desensitization.
Original languageEnglish
Pages (from-to)1591-1598
Number of pages8
JournalInvestigative Ophthalmology and Visual Science
Volume51
Issue number3
DOIs
Publication statusPublished - Mar 2010

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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