Myocardial contractility represents the innate ability of the heart muscle (cardiac muscle or myocardium) to contract. The ability to produce changes in force during contraction result from incremental degrees of binding between different types of tissue, that is, between filaments of myosin (thick) and actin (thin) tissue. The degree of binding depends upon the concentration of calcium ions in the cell. Within an in vivo intact heart, the action/response of the sympathetic nervous system is driven by precisely timed releases of a catecholamine, which is a process that determines the concentration of calcium ions in the cytosol of cardiac muscle cells. The factors causing an increase in contractility work by causing an increase in intracellular calcium ions (Ca++) during contraction. Mechanisms for altering contractility Increasing contractility is done primarily through increasing the influx of calcium or maintaining higher calcium levels in the cytosol of cardiac myocytes during an action potential. This is done by a number of mechanisms: Sympathetic activation. Increased circulating levels of catecholamines (which can bind to β-Adrenergic activation) as well as stimulation by sympathetic nerves (which can release norepinepherine that binds to β1-adrenoceptors on myocytes) causes the Gs subunit of the receptor to render adenylate cyclase activated, resulting in increase of cAMP - which has a number of effects including phosphorylating phospholamban (via Protein kinase A). Phosphorylating phospholamban. When phospholamban is not phosphorylated, it inhibits the calcium pumps that pump calcium back into the sarcoplasmic reticulum. When it's phosphorylated by PKA, levels of calcium stored in the sarcoplasmic reticulum are increased, allowing a higher rate of calcium being released at the next contraction. However, the increased rate of calcium sequestration also leads to an increase in lusitropy. Sensitizing troponin-C to the effects of calcium. Phosphorylating L-type calcium channels. This will increase their permeability to calcium, allowing more calcium into the myocyte cells, increasing contractility. An abrupt increase in afterload can cause a small increase in inotropy (Anrep effect) by a mechanism that is not fully understood. An increase in heart rate also stimulates inotropy (Bowditch effect; treppe; frequency-dependent inotropy). This is probably due to the inability of Na+/K+-ATPase to keep up with the sodium influx at the higher frequency of action potentials at elevated heart rates Drugs. Drugs like digitalis can act as a positive inotropic agent by inhibiting the Na+/K+ pump. High Na+ concentration gradient is necessary to pump out sarcoplasmic calcium via the Na+/Ca++ antiporter.