ROLE OF NCX1 IN EPICARDIAL CALCIUM DYNAMICS AND ELECTRICAL SIGNALING
- Author(s): Petrosky, Azade Dominique
- Advisor(s): Escobar, Ariel L
- et al.
The Na+/Ca2+ exchanger (NCX1) plays an important role in defining cardiac function by regulating the contractility and excitability of the heart. The aim of my research was to study the effect of impairing NCX1 with various LiCl concentrations (Na+ replaced by Li+), known NCX blockers KBR-7943 and SEA0400 in wild-type intact mouse hearts. In addition to this, cardiac-specific NCX1 KO mice were used to further evaluate intracellular Ca2+ dynamics and the electrical properties of the heart. We hypothesized that impairment of the exchanger would lead to an increase of Ca2+ in the cytosol and consequently an accumulation of Ca2+in the sarcoplasmic reticulum (SR). This accumulation will result in a larger release of Ca2+from the SR. In addition to this, NCX1 impairment will lead to a change in the membrane potential during the repolarization phase of epicardial action potentials. Experiments performed in this dissertation were by the use of a modified version of the pulsed local-field fluorescent microscopy (PLFFM), where hearts were loaded with Ca2+ sensitive fluorescent dyes (rhod-2, AM and mag-fluo-4, AM) or the potentiometric dye (DI-8ANEPPS). Microelectrode impalement for epicardial action potential recordings were also used in this dissertation for simultaneous recordings of intracellular Ca2+ dynamics and left ventricular transmural electrocardiographic recordings. To conclude, impairment of the NCX1 alters intracellular Ca2+ dynamics and changes the electrical properties of the heart.