Normally the Ca concentration in the cardiac cytosol during systole is such that the contractile sites are half activated. Thus the heart has considerable contractile reserve which can be used by increasing the Ca occupancy of the Tn-C binding sites.
Beta adrenergic stimulation is the common method of increasing cytosolic Ca by increasing the flow of Ca across the Ca channel (L type) into the cell. This is mediated by increasing cytosolic cAMP.
Inhibiting the degradation of cAMP (the second messenger of beta stimulation) also increases cytosolic Ca. Phosphodiesterase degrades cytosolic cAMP. Phosphodiesterase inhibitors thus increase cAMP.
Blocking the Na/K-ATPase pump increases cytosolic Ca. As Na accumulates in the cell in the face of an inhibited Na/K pump, Na is extruded from the cell by way of the Na/Ca exchange mechanism and Ca accumulates in the cell. Digoxin functions by blocking the Na/K ATPase pump.
Independent of increasing cytosolic Ca, contractility can be enhanced by increasing the affinity of Tn-C for Ca. Calcium sensitizers function this way (e.g. Pimobendan).
ATP is required for the process of attachment and detachment. The terminal phosphate bond of ATP is split off by myosin ATPase releasing energy for attachment.
Crossbridging is inhibited at rest by both the avid binding of Tn-T and tropomyosin that promotes the positioning of the tropomyosin molecule which is twisted in such a way blocking the interaction of the myosin heads with actin.
The binding of Ca to the Tn-C results in:
d. Chronotropy: refers to the ability to increase heart rate.
e. Lusitropy: refers to the ability of the heart to relax.
f. Dromotropy: refers to the speed of conduction.