High resolution

Module 2: Figure pyruvate and Ca2+ signalling

The effect of pyruvate on Ca2+ signalling in cardiac myocytes.

The traces represent the Ca2+ spikes that are generated when isolated cardiac myocytes are electrically stimulated at 0.5 Hz. Under control conditions (0'), there are constant amplitude transients resulting from the release from the internal store. The size of this store is indicated by the amplitude of the much larger transient when caffeine (10 mM) is added. The next series of transients were taken 1, 2 and 8 min after addition of 10 mM pyruvate, which caused an increase in both the resting level and the transient amplitudes. This increase in the amplitude of the Ca2+ transients may have resulted from an increase in the content of the internal store, as indicated by the very large caffeine-induced transient apparent at the end of the 8-min sequence. The effect of pyruvate was reversible because the signalling system was back to its control values 4 min after washing out the pyruvate (W). A possible interpretation of this experiment is that pyruvate enhanced metabolism and the increase in ATP concentration may have enhanced the formation of cyclic ADP-ribose (cADPR) to stimulate the pump that transfers Ca2+ into the internal store (Module 2: Figure cADPR/NAADP function). Reproduced from Zima, A.V., Kockskämper, J., Meijia-Alvarez, R. and Blatter, L.A. (2003) Pyruvate modulates cardiac sarcoplasmic reticulum Ca2+ release in rats via mitochondria-dependent and -independent mechanisms. J. Physiol. 550:765–783, with permission from Blackwell Publishing; see Zima et al. 2003.