Follow the calcium. – cardiomyocyte calcium handling quick notes

Big Picture: Calcium is responsible for the inotropic effect by facilitating the formation of cross-bridges between the myosin heads and the actin filaments.

1. Depolarization induced calcium release.
   1. L-type calcium channel (DHP channel) activation causes calcium influx into the cardiomyocyte. 
      1. This is the same L-type calcium channel that is responsible for plateau of the cardiomyocyte action potential.
2. Calcium induced calcium release.
   1. Increased intracellular calcium near the sarcoplasmic reticulum(SR) activates calcium release from the SR via the RYR2 channel.
   2. The intracellular calcium concentration rises from ~0 μmol, to 1 μmol.
      1. Makes sense because if there was no increase in the amount of calcium there would be no muscle contraction. On the other hand, the intracellular calcium concentration needs to decrease significantly to induce relaxation.
      2. The intracellular calcium concentration is directly correlated to the inotropic effect because calcium association with troponin C(TnC) results in an increase in actin binding sites which creates more cross-bridges with myosin heads, and therefore a stronger contraction.
3. Now that the calcium concentration has increased in the cardiomyocyte and contraction has occurred, it gets sequestered from interacting with TnC though the actions of PKA.
   1. PKA will phosphorylate TnC and decrease the affinity of TnC and calcium.
   2. PKA will also phosphorylate phospholamban and cause it to dissociate from the Serca(ATPase) channels on the SR, thereby activating it. 
      1. When activated, the Serca channels will bring calcium from the cytoplasm back into the SR.
   3. Cell membrane channels utilize primary active(ATPase) and secondary active transport(Sodium-calcium exchange) to move calcium out of the cell.
4. The cycle starts over at 1.