Ca2+ ions are well known to be the universal but unique signaling players in living cells. In cardiac myocytes, Ca2+ can not only regulate gene expression in a relative slow manner (in a time scale of minutes or hours), as is present in most other cell types, but also function as direct coupler between the fast electrical action potential and mechanical contraction (in sub-second scale). This tight functional excitation-contraction coupling (EC-coupling) is the basis of heart beating. The fast Ca2+ signaling in EC-coupling and the slow Ca2+ signaling in regulating gene expression within the same cardiomyocyte are perfectly tuned, such that one Ca2+ signaling does not interfere with the other. Mere interestingly, the two isolated processes can regulate each other in a manageable manner. The two Ca2+ signaling processes are involved in cardiac disease, e.g. heart failures. Understanding the cardiac Ca2+ signaling mystery will facilitate the cure of cardiac diseases.
To understand the mystery of Ca2+ signaling in cardiomyocytes, we are investigating the elementary Ca2+ release units (CRU) in electrically stimulated Ca2+ transient of cardiomyocytes. We first isolate the elementary Ca2+ releases from these CRUs in cardiac Ca2+ transients with advanced methodology, and then we further quantify the effects of either physiological or pathological conditions that are applied on these CRUs, e.g. the slow Ca2+ signaling via IP3 receptors, adrenergic stimulation, or in the condition of heart hypertrophy or heart failure.
Ca2+ signals were recorded with either a confocal microscope (Visitech Infinity3) or with iSIM (Visitech), and the recording speed was set to as high as possible, normally 125 ~ 150 Hz.
The recorded Ca2+ signals were analyzed with self-developed CaCLEAN algorithm (eLife 2017 Nov 14;6. pii: e30425), as illustrated below:
Here is a sample results from these analysis: