Physiology for MRCEM Primary

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Basic cellular physiology

Cardiac muscle physiology

[box type=”download”]  Functional differences from skeletal muscle  Concept of electrical coupling in cardiac muscle cells  Calcium release mechanisms  Relation between length and tension (Starling relationship) in cardiac muscle  Note: smooth muscle physiology is NOT required knowledge[/box]

The myocardium is composed of cardiac muscle cells called myocytes.
These cells are striated due to the orderly arrangement of the thick and thin filaments which, as in skeletal muscle, make up the bulk of the muscle.
The myocytes are branched, with a single nucleus, and are also rich in mitochondria.
Their contraction is not dependent on an external nerve supply (inherent rhythmicity).
The nerves innervating the heart only speed up or slow down the rhythm and can modify the force of contraction (termed chronotropic and inotropic effects respectively).
The synchronicity between myocytes occurs because all adjacent cells are linked to one another at their ends by specialized gap junctions (formed of connexons) within the intercalated discs, which essentially provide low-resistance electrical pathways between cells.
These allow action potentials to spread rapidly between cells and enable the cardiac muscle to act as a functional syncytium.
The intercalated discs also provide structural attachments (desmosomes) between myocytes to distribute force.
Although a rise in intracellular Ca2+ initiates contraction in the same way as in skeletal muscle, the mechanisms leading to this rise in intracellular Ca2+ are fundamentally different.

Cardiac muscle electrophysiology

The resting potential of ventricular myocytes is approximately −90 mV (close to EK) and stable (phase 4).
An AP is initiated when the myocyte is depolarized to a threshold potential of approximately −65 mV.
Fast, voltage-gated Na+ channels are activated, leading to an inward current which rapidly depolarizes the membrane towards +30 mV.
This initial depolarization or upstroke (phase 0) is similar to that in nerve and skeletal muscle, and assists transmission to the next myocyte.
The Na+ current rapidly inactivates, but, in cardiac myocytes, the initial depolarization activates voltage-gated Ca2+ channels (L-type channels; threshold approximately −45 mV), through which Ca2+ floods in.
The resultant inward current causes a plateau phase (phase 2) until the L-type channels inactivate.
The cardiac AP is much longer than that in nerve or skeletal muscle (∼300ms vs ∼2 ms).
Repolarization is facilitated by activation of voltage-gated delayed rectifier K+ channels (phase 3).
The plateau and associated Ca2+ entry are essential for contraction; blockade of L-type channels (e.g. dihydropyridines – Ca2+ channel blockers) reduces force.
As the AP lasts almost as long as contraction, its refractory period prevents another AP being initiated until the muscle relaxes; thus cardiac muscle cannot exhibit tetanus.


Ca2+ entry during the AP is essential for contraction, but it only accounts for ∼25% of the rise in intracellular Ca2+.
The rest is released from Ca2+ stores in the sarcoplasmic reticulum (SR).
APs travel down invaginations of the sarcolemma called T-tubules, which are close to the terminal cisternae of the SR.
During the AP plateau, Ca2+ enters the cell and activates Ca2+-sensitive Ca2+ release channels (ryanodine receptors, RyR) in the SR, allowing stored Ca2+ to flood into the cytosol; this is Ca2+- induced Ca2+ release (CICR).

Starling’s law – Check cardiac output lesson under CVS physiology


Ca2+ is rapidly pumped back into the SR (sequestered) by the sarco/endoplasmic reticulum Ca2+ ATPase (SERCA).
The Ca2+ that entered the myocyte during the AP will be removed by the Na+–Ca2+ exchanger (NCX) in the membrane, which pumps one Ca2+ ion out in exchange for three Na+ ions, using the Na+ electrochemical gradient as an energy source.
This is slow, and continues during diastole. If diastole is shortened, i.e. when the heart rate rises, more Ca2+ is left inside the cell and the cardiac force increases. This is the staircase or Treppe effect.