Polymeric nanoparticles like chitosan nanoparticles may be used to deliver drugs to particular organs, such as heart. However, due to the lack of information about acute effects of chitosan nanoparticles in cardiac calcium handling, we evaluated the same in intact rat left ventricular myocytes. Chitosan nanoparticles were synthesized by ionic gelation method for three different concentrations of chitosan and tripolyphosphate (TPP) such as 1:1, 2:1 and 3:1, respectively. The size of the particles was below 100 nm for the 2:1 and 3:1 chitosan:TPP ratio and 300 nm for 1:1 ratio. The particles synthesized in 3:1 ratio were incubated for 0, 15, 30 and 60 minutes with Fluo-3 loaded cardiomyocytes, their effects were evaluated in local Ca2+ release events using confocal microscopy and compared with control cells. Chitosan nanoparticles increased the amplitude and size of Ca2+ spark by 14.1% and 24.1% at 30 minutes of incubation; while the increment was 24.7% and 28.4% at 60 minutes respectively. Accordingly, rising time of Ca2+ sparks was decreased by 47% at 30 minutes. These changes were reflected in increased local Ca2+ flux by 58.3% and spark-mediated Ca2+ leak by 145.9% and 146.5% at 30, and 60 minutes, respectively. Hence, these results indicate that chitosan nanoparticles modify the properties of local Ca2+ release events mainly at short incubation times and must be taken into account while using these nanoparticles in drug delivery.
The participation of the ionic Ca(2+) release channel/ryanodine receptor in cardiac excitation-contraction coupling is well known since the late '80s, when various seminal papers communicated its purification for the first time and its identity with the "foot" structures located at the terminal cisternae of the sarcoplasmic reticulum. In addition to its main role as the Ca(2+) channel responsible for the transient Ca(2+) increase that activates the contractile machinery of the cardiomyocytes, the ryanodine receptor releases Ca(2+) during the relaxation phase of the cardiac cycle, giving rise to a diastolic Ca(2+) leak. In normal physiological conditions, diastolic Ca(2+) leak regulates the proper level of luminal Ca(2+), but in pathological conditions it participates in the generation of both, acquired and hereditary arrhythmias. Very recently, several groups have focused their efforts into the development of pharmacological tools to control the altered diastolic Ca(2+) leak via ryanodine receptors. In this review, we focus our interest on describing the participation of cardiac ryanodine receptor in the diastolic Ca(2+) leak under physiological or pathological conditions and also on the therapeutic approaches to control its undesired exacerbated activity during diastole.
We also investigated how RyR2 mutations associated with catecholaminergic polymorphic ventricular tachycardia (CPVT) influence the dynamics of Ca 2þ sparks, ''invisible'' non-spark Ca 2þ leak, [Ca 2þ ] i transients, and SR Ca 2þ content. We observe that CPVT mutations can lead to unstable Ca 2þ spark dynamics, altering SR Ca 2þ content and promoting [Ca 2þ ] i signaling instability. Our new model provides significant insights into the dynamics of local control of CICR under physiological and pathological conditions.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.