CaMKII protects the heart from intracellular acidosis but becomes deleterious upon returning to normal pH

MUNDIÑA - WEILENMANN C

Merced, CA

Seminario; Invitada a la Universidad de California, Merced School of Engineering; 2009

Universidad de California, Merced School of Engineering

Intracellular acidosis exerts substantial effects on the contractile performance of the heart. Soon after the onset of the acidosis-induced decrease in contractility, there is a progressive recovery of developed force that occurs despite the persistent acidosis. This recovery is the result of different mechanisms that converge to increase diastolic Ca2+ levels and Ca2+ transient amplitude. The multifunctional Ca2+/calmodulin-dependent protein kinase II (CaMKII) is an essential step in the sequence of events that leads to the increase in the Ca2+ transient amplitude and produces the contractile recovery. CaMKII may act as an amplifier, providing compensatory pathways to offset the inhibitory effects of acidosis on many of the Ca2+ handling proteins. However, upon returning to normal pH, these CaMKII triggered mechanisms become deleterious and promote the appearance of arrhythmias. The intracellular processes responsible for the functional consequences of CaMKII activation will be discussed.