Crosstalk between L-type Ca2+ channels and the sarcoplasmic reticulum: alterations during cardiac remodelling.
In the cardiac dyad, sarcolemmal L-type Ca(2+) channels (LCCs) and sarcoplasmic reticulum (SR) Ca(2+) release channels (RyR) are structurally in close proximity. This organization provides for an efficient functional coupling, tuning SR Ca(2+) release for optimal contraction of the myocyte. Given that LCC are regulated by the prevailing [Ca(2+)], this structural organization is the setting for feedback mechanisms and crosstalk. A defective coupling of Ca(2+) influx via LCC to activation of RyR has been implicated in reduced SR Ca(2+) release in heart failure. Both functional changes in LCC properties and structural re-organization of LCC in T-tubules could be involved. LCC are regulated by cytosolic Ca(2+), and crosstalk with SR Ca(2+) handling occurs on a long-term basis, i.e. during steady-state changes in heart rate, on an intermediate-term basis, i.e. on a beat-to-beat basis during sudden rate changes, and on a very short- or immediate-term basis, i.e. during a single heartbeat. We review the properties and consequences of these different feedback mechanisms and the changes in heart failure and cardiac hypertrophy that have thus far been studied.
Bito
Virginie
V
Department of Cardiovascular Medicine, Division of Experimental Cardiology, University of Leuven, KUL Campus Gasthuisberg O/N 7th floor, Herestraat 49, B-3000 Leuven, Belgium.
Heinzel
Frank R
FR
Biesmans
Liesbeth
L
Antoons
Gudrun
G
Sipido
Karin R
KR
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology; D002118:Calcium / Q000378:metabolism; D020746:Calcium Channels, L-Type / Q000502:physiology*; D006332:Cardiomegaly / Q000378:metabolism*; D025461:Feedback, Physiological; D006333:Heart Failure / Q000378:metabolism*; D006339:Heart Rate; D006801:Humans; D009200:Myocardial Contraction; D019837:Ryanodine Receptor Calcium Release Channel / Q000502:physiology; D012519:Sarcoplasmic Reticulum / Q000502:physiology*
D020746:Calcium Channels, L-Type; D019837:Ryanodine Receptor Calcium Release Channel; D002118:Calcium