The Bowditch effect, also known as the Treppe phenomenon and the Treppe effect, is an

autoregulation Autoregulation is a process within many biological systems, resulting from an internal adaptive mechanism that works to adjust (or mitigate) that system's response to stimuli. While most systems of the body show some degree of autoregulation, it ...

method by which myocardial tension increases with an increase in

heart rate Heart rate (or pulse rate) is the frequency of the heartbeat measured by the number of contractions (beats) of the heart per minute (bpm). The heart rate can vary according to the body's physical needs, including the need to absorb oxygen and excr ...

. It was first observed by Henry Pickering Bowditch in 1871.

Mechanism

The underlying cause of the Bowditch effect is an increase in the

calcium Calcium is a chemical element with the symbol Ca and atomic number 20. As an alkaline earth metal, calcium is a reactive metal that forms a dark oxide-nitride layer when exposed to air. Its physical and chemical properties are most similar ...

concentration in the

sarcoplasmic reticulum The sarcoplasmic reticulum (SR) is a membrane-bound structure found within muscle cells that is similar to the smooth endoplasmic reticulum in other cells. The main function of the SR is to store calcium ions (Ca2+). Calcium ion levels are ke ...

cardiac muscle cell Cardiac muscle (also called heart muscle, myocardium, cardiomyocytes and cardiac myocytes) is one of three types of vertebrate muscle tissues, with the other two being skeletal muscle and smooth muscle. It is an involuntary, striated muscle tha ...

s, and its increased release into sarcoplasm. One of the explanations for an increase in the intracellular calcium concentration is the inability of the Na⁺/K⁺-ATPase to keep up with influx of

sodium Sodium is a chemical element with the symbol Na (from Latin ''natrium'') and atomic number 11. It is a soft, silvery-white, highly reactive metal. Sodium is an alkali metal, being in group 1 of the periodic table. Its only stable ...

at higher

s. When a higher heart rate occurs, for example due to adrenergic stimulation, the L-type calcium channel has increased activity. The

sodium-calcium exchanger The sodium-calcium exchanger (often denoted Na+/Ca2+ exchanger, exchange protein, or NCX) is an antiporter membrane protein that removes calcium from cells. It uses the energy that is stored in the electrochemical gradient of sodium (Na+) by al ...

(which allows 3 Na⁺ to flow down its

electrochemical gradient An electrochemical gradient is a gradient of electrochemical potential, usually for an ion that can move across a membrane. The gradient consists of two parts, the chemical gradient, or difference in solute concentration across a membrane, and ...

in exchange for 1 Ca⁺⁺ ion to flow out of the cell) works to decrease the levels of intracellular calcium. As the heart rate becomes more robust, and the length of

diastole Diastole ( ) is the relaxed phase of the cardiac cycle when the chambers of the heart are re-filling with blood. The contrasting phase is systole when the heart chambers are contracting. Atrial diastole is the relaxing of the atria, and ventri ...

decreases, the Na⁺/K⁺-ATPase, which removes the Na⁺ brought into the cell by the Na⁺/Ca⁺⁺ exchanger, does not keep up with the rate of Na⁺ influx. This leads to a less efficient Na⁺/Ca⁺⁺ exchange, since the gradient is decreasing for sodium and the driving force behind calcium transport is actually the

concentration gradient Molecular diffusion, often simply called diffusion, is the thermal motion of all (liquid or gas) particles at temperatures above absolute zero. The rate of this movement is a function of temperature, viscosity of the fluid and the size (mass) o ...

of sodium, therefore Ca⁺⁺ builds up within the cell. This results in an accumulation of calcium in the myocardial cell via the

sodium calcium exchanger The sodium-calcium exchanger (often denoted Na+/Ca2+ exchanger, exchange protein, or NCX) is an antiporter membrane protein that removes calcium from cells. It uses the energy that is stored in the electrochemical gradient of sodium (Na+) by al ...

and leads to a greater state of inotropism, a mechanism which is also seen with

cardiac glycoside Cardiac glycosides are a class of organic compounds that increase the output force of the heart and decrease its rate of contractions by inhibiting the cellular sodium-potassium ATPase pump. Their beneficial medical uses are as treatments for c ...

s. Alternatively, another mechanism is that the Na⁺-Ca⁺⁺ membrane exchanger, which operates continually, has less time to remove the Ca⁺⁺ that arrives in the cell. This occurs because of the decreased length of diastole with positive

chronotropy Chronotropic effects (from ''chrono-'', meaning time, and ''tropos'', "a turn") are those that change the heart rate. Chronotropic drugs may change the heart rate and rhythm by affecting the electrical conduction system of the heart and the ne ...

. With an increased intracellular Ca⁺⁺ concentration, there follows a positive

inotropy An inotrope is an agent that alters the force or energy of muscular contractions. Negatively inotropic agents weaken the force of muscular contractions. Positively inotropic agents increase the strength of muscular contraction. The term ''inotr ...

.''Physiology at a Glance'', Second Edition (2008) — Jeremy Ward & Roger Linden It has also been observed that increased heart rate stimulates SERCA2a, which increases the calcium inflow and content in the sarcoplasmic reticulum. This activation of SERCA2a is indirectly by the phosphorylation of

phospholamban Phospholamban, also known as PLN or PLB, is a micropeptide protein that in humans is encoded by the ''PLN'' gene. Phospholamban is a 52-amino acid integral membrane protein that regulates the calcium (Ca2+) pump in cardiac muscle cells. Funct ...

(PLN) by calmodulin kinase II (

CAMK CAMK, also written as CaMK or CCaMK, is an abbreviation for the Ca2+/calmodulin-dependent protein kinase class of enzymes. CAMKs are activated by increases in the concentration of intracellular calcium ions (Ca2+) and calmodulin. When activated, t ...

Clinical significance

Positive Bowditch effect causes an increase in cardiac output due to the increased force of contraction of heart muscles. This phenomenon is usually absent or even reversed (negative Bowditch effect) in heart failure and other diseases of heart, such as cardiomyopathy and coronary artery disease. This is termed as the null or inverse staircase phenomenon. The probable cause for this effect is attributed to mutations in SERCA2a.

History

The Bowditch effect was first observed by Henry Pickering Bowditch in 1871, after whom it is named.

References

{{reflist Cardiovascular diseases