Cardiomyocytes contract against a mechanical load during each heartbeat, and excessive mechanical stress leads to heart diseases. Using a cell-in-gel system that imposes an afterload during cardiomyocyte contraction, we found that nitric oxide synthase (NOS) was involved in transducing mechanical load to alter Ca2+ dynamics. In mouse ventricular myocytes, afterload increased the systolic Ca2+ transient, which enhanced contractility to counter mechanical load, but also caused spontaneous Ca2+ sparks during diastole that could be arrhythmogenic. The increases in the Ca2+ transient and sparks were attributable to increased ryanodine receptor (RyR) sensitivity because the amount of Ca2+ in the sarcoplasmic reticulum load was unchanged. Either pharmacological inhibition or genetic deletion of nNOS (or NOS1), but not of eNOS (or NOS3), prevented afterload-induced Ca2+ sparks. This differential effect may arise from localized NO signaling, arising from the proximity of nNOS to RyR, as determined by super-resolution imaging. Ca2+-calmodulin–dependent protein kinase II (CaMKII) and nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2) also contributed to afterload-induced Ca2+ sparks. Cardiomyocytes from a mouse model of familial hypertrophic cardiomyopathy exhibited enhanced mechanotransduction and frequent arrhythmogenic Ca2+ sparks. Inhibiting nNOS and CaMKII, but not NOX2, in cardiomyocytes from this model eliminated the Ca2+ sparks, suggesting mechanotransduction activated nNOS and CaMKII independently from NOX2. Thus, our data identify nNOS, CaMKII, and NOX2 as key mediators in mechanochemotransduction during cardiac contraction, which provides new therapeutic targets for treating mechanical stress–induced Ca2+ dysregulation, arrhythmias, and cardiomyopathy.

Comparison of the steady-state FTIR absorption spectra of coumarin-102 (C-102) in tetrachloroethylene with added aniline of various concentrations, in neat aniline and in neat N,N-dimethylaniline (DMA), indicates formation of a hydrogen-bonded complex between C-102 and aniline in solution. Subpicosecond time-resolved infrared absorption spectroscopy has been applied to study the dynamics of the hydrogen-bond following photoexcitation of C-102 chromophore in a C-102-aniline hydrogen-bonded complex. Upon photoexcitation at 400 nm, the hydrogen bond between C-102 and aniline breaks within 250 fs. Reformation of hydrogenbond between the excited C-102 molecule and aniline takes place within about 30 ps. Biexponential temporal dynamics monitored at CdO stretching vibration (1736-1742 cm -1 ) in neat aniline, which is a strongly structured solvent due to formation of intermolecular hydrogen bonds, reveals the biphasic solvation dynamics of aniline with solvation times 0.6 and 7.2 ps. These time constants have been assigned to nondiffusive and diffusive structural reorganization of the solvent. † Part of the special issue "Charles S. Parmenter Festschrift".

Third-order nonlinear optical properties of two series of self-assembled porphyrin wires, one being terminated by zinc porphyrin and the other by free base porphyrin, were measured by femtosecond time-resolved optical Kerr effect. The hyperpolarizability values of the latter series were extremely large ranging from 10-30 to 10-29 esu, 10 times larger than the former. The behavior is accounted for by the contribution of terminal free base porphyrin to enhance the molecular polarization by acceptor nature toward central metalloporphyrin array.