Cardiac muscle relaxation occurs when intracellular Ca2+ levels return to baseline. Since Ca2+ enters the cytoplasm to trigger contraction, it must then leave the cytoplasm to return to baseline.
After the myocyte is depolarized, L-type Ca2+ channels (long-acting, voltage gated, active in Phase 2 of the action potential) open to allow Ca2+ to enter the cell, which leads to calcium-induced-calcium-release (CICR) via the ranyodine receptor (ligand gated, active in Phase 2 as well), a phenomenon unique to cardiac myocytes (compared to skeletal muscle). Eventually, intracellular Ca2+ binds troponin, which allows actin and myosin to bind and contract. To relax, Ca2+ leaves the cytoplasm via several mechanisms: 1) the Na+/Ca2+ exchanger, which allows 1 Ca2+ to exit for every 3 Na+ that enter, 2) the Ca2+ ATP-ase pump in the cell membrane, which pumps Ca2+ out of the cell, and 3) the Ca2+ ATP-ase pump in the sarcoplasmic reticulum (SR) membrane, which pumps Ca2+ into the SR.
Bhattacharya argues that calcium supplementation is not detrimental to heart health. Although calcium is essential to heart physiology, recent studies have led to uncertainty regarding whether widespread calcium supplementation (to prevent osteoporosis) is increasing atherosclerotic disease. The data that has been used to support this argument thus far has not been collected in a systematic way and the studies used in meta-analyses were not designed to assess atherosclerosis as a primary endpoint.
Kojima et al. recently investigated the physiologic mechanism underlying the cardioprotective effects of an inhaled anesthetic, sevoflurane, using a mouse model. They found that sevoflurane protected against oxidative injury via altering several calcium channels: ICa,L, the Na+/Ca2+ exchanger and the ryanodine receptor. This work has implications for preventing reperfusion injury.
Illustration A shows cardiac muscle under a microscope. Illustration B depicts the channels, ions, and cellular compartments important in excitation contraction coupling.
Answers 1 & 2: K+ actually must enter the myocyte and Na+ must leave it (via Na+/K+ ATPase) to establish the Na+ gradient that drives the Na+/Ca2+ exchanger.
Answers 3 & 4: Ca2+ must enter the cell, first from outside the myocyte, and then from the SR (via CICR) for the cell to contract, but not to relax.
Bhattacharya RK. Does widespread calcium supplementation pose cardiovascular risk? No: concerns are unwarranted. Am Fam Physician. 2013 Feb 1;87(3):Online.
PMID:23418771 (Link to Abstract)
Kojima A, Kitagawa H, Omatsu-Kanbe M, Matsuura H, Nosaka S. Sevoflurane protects ventricular myocytes against oxidative stress-induced cellular Ca(2+) overload and hypercontracture. Anesthesiology. 2013 Sep;119(3):606-20.
PMID:24137676 (Link to Abstract)