Multimodality of Ca2+ signaling in rat atrial myocytes

It has been suggested that the multiplicity of Ca2+ signaling pathways in atrial myocytes may contribute to the variability of its function. This article reports on a novel Ca2+ signaling cascade initiated by mechanical forces induced by "puffing" of solution onto the myocytes. Cat 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 (similar to 300 ms) developing Ca-i transients that lasted 1,693 +/- 68 ms at room temperature. Subsequent second and third puffs, applied at similar to 20 s intervals activated significantly smaller or no Cai transients. Puff-triggered Cai transients could be reactivated once again following caffeine (10 mM)-induced release of Ca2+ from sarcoplasmic reticulum (SR). Puff-triggered Cai transients were independent of [Ca2+](o), and activation of voltage-gated Ca2+ or cationic stretch channels or influx of Ca2+ on Na+/Ca(2+)exchanger, because puffing solution containing no Ca2+, 10 mu M diltiazem, 1 mM Cd2+, 5 mM Ni2+, or 100 mu M Gd3+ failed to suppress them. Puff-triggered Cai transients were enhanced in paced compared to quiescent myocytes. Electrically activated Cai transients triggered during the time course of puff-induced transients were unaltered, suggesting functionally separate Ca2+ pools. Contribution of inositol 1,4,5-triphosphate (IP3)-gated or mitochondrial Ca2+ pools or modulation of SR stores by nitric oxide/nitric oxide synthase (NO/NOS) signaling were evaluated using 0.5 to 500 mu M 2-aminoethoxydiphenyl borate (2-APB) and 0.1 to 1 mu M carbonylcyanide-p-trifluoromethoxyphenylhydrazone (FCCP), and 1 mM N omega-Nitro-L-arginine methyl ester (L-NAME) and 7-nitroindizole, respectively. Only FCCP appeared to significantly suppress the puff-triggered Cai transients. It was concluded that neither Ca2+ 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 Ca2+ from a limited Ca2+ store of mitochondria. How mechanical forces are sensed and transmitted to mitochondria to induce Ca2+ release and what role such a Ca2+ signaling pathway plays in the physiology or pathophysiology of the heart remain to be worked out.