'Ca(2+)-induced Ca(2+) entry' or how the L-type Ca(2+) channel remodels its own signalling pathway in cardiac cells.
The adjustment of Ca(2+) entry in cardiac cells is critical to the generation of the force necessary for the myocardium to meet the physiological needs of the body. In this review, we present the concept that Ca(2+) can promote its own entry through Ca(2+) channels by different mechanisms. We refer to it under the general term of 'Ca(2+)-induced Ca(2+) entry' (CICE). We review short-term mechanisms (usually termed facilitation) that involve a stimulating effect of Ca(2+) on the L-type Ca(2+) current (I(Ca-L)) amplitude (positive staircase) or a lessening of Ca(2+)-dependent inactivation of I(Ca-L). This latter effect is related to the amount of Ca(2+) released by ryanodine receptors (RyR2) of the sarcoplasmic reticulum (SR). Both effects are involved in the control of action potential (AP) duration. We also describe a long-term mechanism based on Ca(2+)-dependent down-regulation of the Kv4.2 gene controlling functional expression of the repolarizing transient outward K(+) current (I(to)) and, thereby, AP duration. This mechanism, which might occur very early during the onset of hypertrophy, enhances Ca(2+) entry by maintaining Ca(2+) channel activation during prolonged AP. Both Ca(2+)-dependent facilitation and Ca(2+)-dependent down-regulation of I(to) expression favour AP prolongation and, thereby, promote sustained voltage-gated Ca(2+) entry used to enhance excitation-contraction (EC) coupling (with no change in the density of Ca(2+) channels per se). These self-maintaining mechanisms of Ca(2+) entry have significant functions in remodelling Ca(2+) signalling during the cardiac AP. They might support a prominent role of Ca(2+) channels in the establishment and progression of abnormal Ca(2+) signalling during cardiac hypertrophy and congestive heart failure.
Physiopathologie Cardiovasculaire, INSERM U-637, Université Montpellier 1, CHU Arnaud de Villeneuve, 34295 Montpellier Cedex 5, France.
Sylvain
S
Richard
Emeline
E
Perrier
Jérémy
J
Fauconnier
Romain
R
Perrier
Laetitia
L
Pereira
Ana Maria
AM
Gõmez
Jean-Pierre
JP
Bénitah
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020746:Calcium Channels, L-Type / Q000502:physiology*; D006801:Humans; D008564:Membrane Potentials / Q000502:physiology; D032383:Myocytes, Cardiac / Q000502:physiology*; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D015398:Signal Transduction
D020746:Calcium Channels, L-Type; D019837:Ryanodine Receptor Calcium Release Channel; D002118:Calcium