Casq2 deletion causes sarcoplasmic reticulum volume increase, premature Ca²⁺ release, and catecholaminergic polymorphic ventricular tachycardia
J. Clin. Invest. Björn C. Knollmann, et al. 116:2510 doi:10.1172/JCI29128 [Go to this article.]

Figure 4
Casq2^–/– myocytes display spontaneous Ca²⁺ releases and triggered beats but largely maintain normal contractility, SR Ca²⁺ release amplitudes, and SR Ca²⁺ content. (A) Examples of [Ca²⁺]_i transients (top traces) and cell shortening (bottom traces) recorded from fura-2/AM–loaded, field-stimulated myocytes (1 Hz). Application of 1 μmol/l isoproterenol (ISO) significantly increased Ca²⁺ transients and cell shortening in both myocytes. Note that shortly after ISO application was started, only the Casq2^–/– myocyte displayed spontaneous Ca²⁺ releases and aftercontractions of increasing amplitude following each paced twitch (vertical lines). (B and C) Comparison of the incidence of spontaneous (Spont.) Ca²⁺ release events (B) and Ca²⁺ oscillations (C) at baseline and in the presence of ISO. Data represent the fraction (%) of myocytes that displayed at least 1 event during a 20-second recording period. Insets show representative examples of spontaneous Ca²⁺ after-releases (arrows in B, inset) and Ca²⁺ oscillations (C, inset) induced by spontaneous Ca²⁺ releases and triggered beats (# in C, inset). *P < 0.05, **P < 0.01, ^†P < 0.001, Casq2^–/– versus Casq2^+/+ myocytes by Fisher’s exact test. Casq2^+/+ myocytes: n = 45 (baseline) and 27 (ISO); Casq2^–/– myocytes: n = 71 (baseline) and 43 (ISO).