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Multimodality of Ca 2+ Signaling in Rat Atrial Myocytes
Author(s) -
MORAD MARTIN,
JAVAHERI ASHKAN,
RISIUS TIM,
BELMONTE STEVE
Publication year - 2005
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1341.010
Subject(s) - atrial myocytes , myocyte , multimodality , medicine , chemistry , cardiology , computer science , world wide web
A bstract : It has been suggested that the multiplicity of Ca 2+ signaling pathways in atrial myocytes may contribute to the variability of its function. This article reports on a novel Ca 2+ signaling cascade initiated by mechanical forces induced by “puffing” of solution onto the myocytes. Ca i transients were measured in fura‐2 acetoxymethyl (AM) loaded cells using alternating 340‐ and 410‐nm excitation waves at 1.2 kHz. Pressurized puffs of bathing solutions, applied by an electronically controlled micro‐barrel system, activated slowly (∼300 ms) developing Ca i transients that lasted 1,693 ± 68 ms at room temperature. Subsequent second and third puffs, applied at ∼20 s intervals activated significantly smaller or no Ca i transients. Puff‐triggered Ca i transients could be reactivated once again following caffeine (10 mM)‐induced release of Ca 2+ from sarcoplasmic reticulum (SR). Puff‐triggered Ca i transients were independent of [Ca 2+ ] o , and activation of voltage‐gated Ca 2+ or cationic stretch channels or influx of Ca 2+ on Na + /Ca 2+ exchanger, because puffing solution containing no Ca 2+ , 10 μM diltiazem, 1 mM Cd 2+ , 5 mM Ni 2+ , or 100 μM Gd 3+ failed to suppress them. Puff‐triggered Ca i transients were enhanced in paced compared to quiescent myocytes. Electrically activated Ca i transients triggered during the time course of puff‐induced transients were unaltered, suggesting functionally separate Ca 2+ pools. Contribution of inositol 1,4,5‐triphosphate (IP 3 )‐gated or mitochondrial Ca 2+ pools or modulation of SR stores by nitric oxide/nitric oxide synthase (NO/NOS) signaling were evaluated using 0.5 to 500 μM 2‐aminoethoxydiphenyl borate (2‐APB) and 0.1 to 1 μM carbonylcyanide‐p‐trifluoromethoxyphenylhydrazone (FCCP), and 1 mM Nω‐Nitro‐L‐arginine methyl ester (L‐NAME) and 7‐nitroindizole, respectively. Only FCCP appeared to significantly suppress the puff‐triggered Ca i transients. It was concluded that neither Ca 2+ influx nor depolarization was required for activation of this signaling pathway. These studies suggest that pressurized puffs of solutions activate a mechanically sensitive receptor, which signals in turn the release of Ca 2+ from a limited Ca 2+ store of mitochondria. How mechanical forces are sensed and transmitted to mitochondria to induce Ca 2+ release and what role such a Ca 2+ signaling pathway plays in the physiology or pathophysiology of the heart remain to be worked out.