MCB 32 FALL 2000



MCB 32 Fall 2000

CARDIAC MUSCLE AND HEART

SMOOTH MUSCLE AND BLOOD VESSELS

READING: CHAPTER 12, ESPECIALLY PP 170-178 AND CHAPTER 8.

I. Cellular electrical and mechanical activity in heart: Figs 6.21 and 6.22

Mechanism of electrical excitation: action potential. Every beat of the heart has to be preceded by an electrical excitation. Different from skeletal muscle in that the electrical excitation comes from the heart itself, and nerves (autonomic, involuntary) regulate the rate of excitation. Another difference is that excitation of one cardiac cell leads to conduction of the action potential to all the other cells in the heart because the cells are coupled together by gap junctions, which insure electrical continuity between cells. Cardiac cells are also mechanically attached by little spot welds (called desmosomes or intercalated disks) between cells near the gap junctions. These mechanical attachments help to assure that the gap junctions do not fall apart from each other.

Mechanism of cardiac cell contraction: Ca entry into the cytosol due to release of Ca from the SR (stored there due to activity of Ca pump that uses ATP to accumulate Ca to high concentration, in mM range). Ca release from SR is somewhat different from that in skeletal muscle in that SR release sites need to be triggered by Ca entering across the plasma membrane due to opening of Ca channels during the action potential. This “trigger Ca” acts on SR release sites to open them, releasing flood of Ca into the cytosol.

The Ca then operates similar to skeletal muscle:

Ca ( Troponin ( Tropomyosin ( allow actin and myosin to bind and contract

Ca removal following action potential: Ca pump into SR and out across the plasma membrane. Na/Ca exchange (also called an antiporter) in plasma membrane transports Na into cell from outside (where [Na] is high) to inside the cell (where [Na] is low) and Ca from the cytosol (where [Ca] is low) to outside (where [Ca] is high). This also contributes to relaxation.

II. Important aspects of cardiac action potential: gradual depolarization, regulation, and extended duration

Refractory period of skeletal muscle vs cardiac muscle: Fig. 6.23

Periodic contraction and relaxation of cardiac muscle is crucial. It does no good for heart muscle to maintain constant tension/contraction like skeletal muscle can do. How is this periodicity assured?

Longer refractory period of cardiac muscle assures that relaxation will occur before another action potential is generated. Longer refractory period is caused by the longer action potential duration of cardiac muscle.

B. Frequency of action potentials can be modulated by autonomic nervous system: Fig. 8.7

Sympathetic nerves release norepinehrine onto the cells of the heart (including those in the SA node – see below), which speeds rate at which action potentials are generated in the cells, increasing the rate of contraction.

Parasympathetic nerves (primarily the vagus) release acetylcholine onto the cells of the heart (including the SA node – see below), which slows rate of action potentials, slowing rate of contraction of heart.

III. SA node is the cardiac pacemaker; conduction system assures orderly electrical excitation: Fig. 8.6

Coordinated activity of heart is necessary. If electrical activity occurred randomly, contraction would similarly be random, and there would be no possibility for efficient contraction of atria followed by the ventricles.

Electrical activity begins in sino-atial node, which has the capability to generate its own action potentials, at rate of heart beat.

AP ( gap junctions ( electrical excitation followed by contraction throughout the atria.

AP ( AV node and Purkinje fibers, specialized set of fibers with less contractile ability but good transmission capability.

Purkinje fibers ( ventricular musculature

IV. Coordinated activity of the heart: Fig. 8.10

SA node action potential ( atria contract Atrial systole

Action potential --> AV node and conducting system ( ventricles contract

Pressure in ventricle rises ( atrio-ventricular valves shut (first heart sound), with no change in volume (isometric or isovolumetric contraction)

Pressure in ventricle > aortic pressure, valve opens, blood ejected (isotonic contraction), arterial pressure rises to systolic level. Ejection phase. Ventricular systole

End of action potential, ventricular musculature relaxes (ventricular diasotle) ( aortic valve closes (second heart sound)

Blood begins to fill atria and ventricles

V. Control of heart rate by autonomic nerves: Fig. 8.8

Control center: medulla oblongata. This region of the brain stem receives information from the peripheral blood pressure monitors, including the pressure receptors in the aorta and large arteries and also in the heart itself.

Sympathetic nerves ( increase rate of depolarization ( increase frequency of AP in SA node. This response occurs during “fight or flight” situations, or during exercise.

Parasympathetic nerves ( decrease rate of depolarization ( reduce frequency of AP in SA node. This response occurs during times when cardiovascular system needs to reduce blood pressure and maintain vegetative state.

VI. Control of cardiac output

CO (liters/min) = stroke volume (ml/beat) x heart rate (beats/min)

Normal human CO = 5 l/min = 72 ml/beat x 70 beats/min

Control by changing heart rate (sympathetic increase, parasympathetic decrease) and stroke volume.

Stroke volume can be changed by altering contractility of heart muscle, usually increased by sympathetic nerves. This increases amount of force generated by the myosin and actin, often through changes in cell [Ca].

Stroke vol also changed by alterations of size of heart (length tension diagram of muscle). This in turn controlled by venous return.

VII. Smooth muscle controls blood vessel contraction

Smooth muscle cells are wrapped around the outsides of blood vessels, which conduct the blood from heart to all the tissues of the body. Constraction of this smooth muscle leads to reduction in the diameter of the vessel, making it harder for blood to flow through. This control permits blood vessels to divert blood to tissues that need extra blood supply (e.g., exercising muscle). This contraction of the vessels is also a way for the system as a whole to control blood pressure, which has to be maintained at a proper level to support blood flow all around the circulatory system, including up to the head.

VIII. Smooth muscle cell structure

As shown in Figs 6.24 and 6.25, smooth muscle cells are quite different from skeletal muscles in that they are not nearly as regularly arranged as skeletal or cardiac muscle. They have one nucleus only, and are therefore capable of dividing, unlike skeletal and cardiac muscle.

Although smooth cells contract using actin and myosin, these proteins are not as well organized as in the other two types of muscle. Actin and myosin “sarcomeres” are arranged at oblique angles to the long axis of the muscle fiber. Actin is attached to the cell membrane of smooth muscle cells at sites called “dense bodies” using specialized proteins. These dense bodies also appear in the cytosol to permit attachments within the cells, similar to the z-lines of skeletal muscle.

Cells are often attached to each other by desmosomes. Some types of smooth muscle have gap junctions between cells which assure that electrical impulses in one cell can be conducted to the next cell to provide coordinated contraction, e.g., smooth muscle in the gastrointestinal tract, which has peristaltic waves that move from one end of the intestine to the other.

IX. Smooth muscle mechanical and electrical activity Figs 6.28 and 6.29

Smooth muscle also has quite different mechanical and electrical properties compared to skeletal and cardiac (see Table 6.3):.

Mechanical contraction is controlled by the entry of Ca into the cells from both outside the cell through Ca channels and also release from the sarcoplasmic reticulum, which is only sparse compared to skeletal and heart muscle. In addition, smooth muscle has two different mechanisms in the SR for releasing Ca: the ryanodine receptor (like cardiac and skeletal muscle) and inositol trisphosphate (IP3) receptor (like in non-excitable cells) are both present. The former release Ca during Ca entry from outside the cell through Ca channels (so-called calcium-induced Ca release) while the latter release Ca in response to hormone and nerve-induced increases in cell [IP3].

Many smooth muscles can contract in the absence of fully developed action potentials. Ca channels in the plasma membrane can be opened without full depolarization as occurs in cardiac and skeletal muscle. Any Ca that enters smooth muscle cytosol from either outside or from the SR leads to increased contraction.

Like cardiac muscle but unlike skeletal muscle, both autonomic nerves (sympathetic release norepinephrine, parasympathetic release acetylcholine) and hormones (e.g., epinephrine) modulate the rates (and strength) of contraction. The automonic nerves innervate the muscles, but the terminals are sort of “strung” along the length of the muscles and are not so well defined as in skeletal muscle. The autonomic nerves often induce action potentials, which are generated by voltage-regulated Ca (not Na) channels. There can also be local regulation by factors released within tissues, e.g., histamine (paracrine action).

Smooth muscle (unlike skeletal muscle) contraction occurs over a very broad range of lengths. This can be seen in Fig. 6.29. This is useful for tissues that must contract under very different conditions, e.g., urinary bladder or stomach (or uterus!) when they are filled compared to when they are quite empty.

Smooth muscle can contract for extended periods of time because it is quite efficient compared to skeletal and cardiac muscle.

Smooth muscle contraction is controlled by Ca, but in a very different way from the way skeletal and cardiac muscle are controlled. It is called myosin-based regulation. A regulatory protein called myosin light chain sits on myosin head and becomes phosphorylated by myosin light chain kinase, which transfers a terminal phosphate from ATP to the MLC. This phosphorylation of MLC allows the actin and myosin to interact, and they will continue to contract (just as in skeletal or cardiac muscle) as long as MLC is phosphorylated. Activity of MLC kinase is in turn controlled by the amount of Ca in the cytosol, with MLC kinase remaining active as long as [Ca] is elevated. During relaxation, [Ca] in the cytosol decreases, MLC kinase is inactivated, and MLC becomes dephosphorylated by MLC phosphatase.

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