Electrophysiological and Contractile Effects of Disopyramide in Patients With Obstructive Hypertrophic Cardiomyopathy: a Translational Study
Raffaele Coppini, Cecilia Ferrantini, Josè Manuel Pioner, Lorenzo Santini, Zhinuo J. Wang, Chiara Palandri, Marina Scardigli, Giulia Vitale, Leonardo Sacconi, Pierluigi Stefàno, Laura Flink, Katherine Riedy, Francesco Saverio Pavone, Elisabetta Cerbai, Corrado Poggesi, Alessandro Mugelli, Alfonso Bueno-Orovio, Iacopo Olivotto and Mark V. Sherrid
Effects of 5 μmol/l of Disopyramide on Ca Sparks in Permeabilized Myocytes
(A) Calcium sparks in permeabilized cardiomyocytes from the left ventricle of transgenic hypertrophic cardiomyopathy mice (R92Q-TnT mutation): the representative kymographic images show confocal line scans traced along the longitudinal cell axis, displaying fluorescence signals from the Ca-selective dye, recorded at a speed of 512 lines/s while bathing the permeabilized myocytes in an intracellular solution containing 150 nmol/l [Ca2+] at room temperature. Spontaneous Ca sparks are visible as spontaneous elevations of local [Ca2+] signal lasting 20 to 40 ms. Representative traces from cells in the absence (left) and presence of disopyramide (Diso) (right) in the bathing solution. Kymographic images are reported in false color (16-colors lookup table) after thresholding and filtering (Gaussian smoothing with 2px sigma). (B) Frequency of spontaneous Ca sparks per 100 μmol/l of scanned line length, in the absence and presence of 5 μmol/l disopyramide. Mean ± SEM from 74 cardiomyocytes (basal) and 63 cardiomyocytes (disopyramide) isolated from 4 mouse hearts. **0.01 > p > 0.001, unpaired Student’s t test.