cAMP/PKA-Dependent Increases in Ca Sparks, Oscillations and SR Ca Stores in Retinal Arteriolar Myocytes after Exposure to Vasopressin

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. Fluo-4-loaded smooth muscle in intact segments of freshly isolated porcine retinal arteriole was imaged by confocal laser micro...

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Published in:Investigative ophthalmology & visual science 2010-03, Vol.51 (3), p.1591-1598
Main Authors: Jeffries, Owen, McGahon, Mary K, Bankhead, Peter, Lozano, Maria Manfredi, Scholfield, C. Norman, Curtis, Tim M, McGeown, J. Graham
Format: Article
Language:English
Subjects:
Aniline Compounds - metabolism
Animals
Antidiuretic Hormone Receptor Antagonists
Arginine Vasopressin - pharmacology
Arterioles - drug effects
Arterioles - metabolism
Caffeine - pharmacology
Calcium - metabolism
Calcium Signaling
Cyclic AMP - metabolism
Cyclic AMP-Dependent Protein Kinases - metabolism
Fluorometry
Fura-2 - metabolism
Indoles - pharmacology
Microscopy, Confocal
Muscle, Smooth, Vascular - drug effects
Muscle, Smooth, Vascular - metabolism
Myocytes, Smooth Muscle - drug effects
Myocytes, Smooth Muscle - metabolism
Pyrrolidines - pharmacology
Receptors, Vasopressin - metabolism
Retinal Artery - drug effects
Retinal Artery - metabolism
Sarcoplasmic Reticulum - metabolism
Swine
Vasoconstrictor Agents - pharmacology
Xanthenes - metabolism
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Summary: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. 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. 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). 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.
ISSN:0146-0404
1552-5783
1552-5783
DOI:10.1167/iovs.09-4401