Zusammenfassung
Ca$^2+$ is a central player in the excitation-contraction coupling
of cardiac myocytes, the process that enables the heart to contract
and relax. Mishandling of Ca$^2+$ is a central cause of both
contractile dysfunction and arrhythmias in pathophysiological conditions
such as heart failure (HF). Upon electrical excitation, Ca$^2+$
enters the myocytes via voltage-gated Ca$^2+$ channels and induces
further Ca$^2+$ release from the sarcoplasmic reticulum (SR).
This raises the free intracellular Ca$^2+$ concentration (Ca$^2+$(i)),
activating contraction. Relaxation is driven by Ca$^2+$(i)
decline, mainly due to re-uptake into the SR via SR Ca$^2+$-ATPase
and extrusion via the sarcolemmal Na$^+$/Ca$^2+$ exchange,
NCX. Intracellular Na$^+$ concentration (Na$^+$(i)) is
a main regulator of NCX, and thus Na$^+$(i) plays an important
role in controlling the cytosolic and SR Ca$^2+$. Na$^+$(i)
may have an even more important role in HF because NCX is generally
upregulated. There are several pathways for Na$^+$ entry into
the cells, whereas the Na$^+$/K$^+$ pump (NKA) is the main
Na$^+$ extrusion pathway and therefore is essential in maintaining
the transmembrane Na$^+$ gradient. Phospholemman is an important
regulator of NKA function (decreasing Na$^+$(i) affinity unless
it is phosphorylated). Here we discuss the interplay between Ca$^2+$
and Na$^+$ in myocytes from normal and failing hearts.
Nutzer