Force-frequency relationship in rat ventricular myocytes; elucidating the intracellular mechanisms

ESPEJO MS; AIELLO IGNACIO; AIELLO EA; DE GIUSTI VC; CIANCIO MC

Buenos Aires

Congreso; 56. XXII ISHR World Congress (International Society for Heart Research); 2016

The force?frequency relationship (FFR) is an important intrinsic regulatory mechanism of cardiac contractility. While an increase in contractile force after elevation of the stimulation frequency (positive FFR) is elicited in ventricular myocytes of most mammalian species, a decrease (negative FFR) or no effect (flat FFR) in contractile force in response to an elevation of the stimulation frequency is also present in some species or pathological situations, including rat and in human heart failure. It is known that reactive oxygen species (ROS) can act as intracellular signaling molecules activating diverse kinases as CaMKII and p38 MAPK. In addition, it was demonstrated that p38 MAPK activation induces a negative inotropic effect in ventricular myocytes mediated by a decrease in myofilament response to Ca2+. The involvement of ROS and p38 MAPK activation during the FFR, however, has not been studied yet. Therefore, our aim was to evaluate the FFR in rat ventricular myocytes and elucidate the intracellular molecules implicated in such process. Cell shortening was recorded with an edge detector in isolated cardiac ventricular myocytes of Wistar rats. The stimulation frequency was set to 0.5, 1 or 2 Hz. In parallel experiments, Ca2+ transient and pHi were also recorded by epifluorescence. Data are shown as percentage change at 2 Hz vs 0.5 Hz. * indicates p