Smooth muscle physiology Flashcards
What is the structure of smooth muscle?
Unlike in skeletal and cardiac muscle, the actin and myosin filaments in smooth muscle are not arranged regularly (Fig 1). As a consequence, smooth muscle does not feature the same cross-striations or striped appearance that is found in skeletal and cardiac muscle (Fig 2).
Smooth muscle contains tropomyosin, but not troponin, which is found in skeletal and cardiac muscle. The cytoplasm contains dense bodies which are comparable to the Z lines of striated muscle, and are bound to actin filaments.
Smooth muscle cells have a single nucleus, but the cell membrane does not have the T-tubule invaginations found in striated muscle. The sarcoplasmic reticulum is poorly developed and there are few mitochondria. Adenosine triphosphate (ATP) is mainly synthesized by glycolysis.
What are the two types of smooth muscle?
Visceral, i.e. single-unit, smooth muscle
Multiunit smooth muscle
Where is smooth muscle found?
Visceral smooth muscle is found in large sheets which are in the walls of blood vessels and hollow viscera such as the gut, uterus, ureters and bladder.
Multiunit smooth muscle is found in structures such as the iris (Fig 2), where fine control of movement is necessary, and also in the walls of large arteries, bronchi and erector pili muscles.
Describe the syncytial function of smooth muscle
Visceral smooth muscle cells are connected by gap junctions which enable action potentials to pass from cell to cell (Fig 1). This means that when one fibre is stimulated by a nerve, hormone or automaticity, the action potential passes sequentially to other muscle cells in the sheet. This syncytial function is similar to cardiac muscle.
In contrast, multiunit smooth muscle consists of individual muscle cells which do not have connecting gap junctions (Fig 2). Each cell or fibre has its own nerve endings.
How is smooth muscle function controlled?
The control of smooth muscle function is involuntary.
Visceral smooth muscle can contract spontaneously or in response to stimulation by autonomic nerves.
Like striated muscle, the contractile process is initiated by a rise in intracellular calcium concentration. Fig 1 contains a series of images showing how a calcium wave travels from the interstitial cell to its adjacent smooth muscle cell.
The calcium wave causes contraction. Actin and myosin filaments slide over each other, with the energy coming from the hydrolysis of ATP. However, there are several differences in the mechanism by which this is achieved.
What is the mechanism of contraction for smooth muscle?
In smooth muscle, the influx of calcium is from the extracellular fluid rather than the sarcoplasmic reticulum.
The calcium ions enter the cell through voltage-gated and ligand-gated channels.
Calcium then binds to a protein called calmodulin, i.e. calcium modulated protein, forming a complex which activates calmodulin-dependent light chain kinase.
Light chain kinase catalyses the phosphorylation of the myosin head and allows myosin ATPase to be activated.
Hydrolysis of ATP provides the energy for the formation of actin-myosin cross-bridges, and actin filaments to slide on myosin to produce muscle contraction.
Describe the speed of contraction in smooth muscle?
Remember that in striated muscle, calcium is released from the sarcoplasmic reticulum when an action potential travels down a T-tubule. Contraction in striated muscle is initiated by calcium binding to troponin C.
Contraction in smooth muscle takes longer to develop and lasts longer than in striated muscle (Fig 1).
One reason for this is that smooth muscle lacks T-tubules and sarcoplasmic reticulum, which means that it takes longer for calcium to diffuse into filaments deeper in the fibre.
The mechanism of contraction is also slower in smooth muscle.
What is the mechanism for relaxation of smooth muscle?
Relaxation occurs when the calcium-calmodulin complex dissociates, as calcium is pumped out of the cytoplasm and myosin is dephosphorylated by myosin light chain phosphatase.
The actin-myosin cross-bridges may remain attached for a period after cytoplasmic calcium concentration falls and myosin is dephosphorylated. This is the latch-bridge mechanism. It produces a sustained contraction with relatively low energy expenditure.
What is plasticity?
If smooth muscle is stretched, its tension initially increases, but then it decreases and may fall below the initial level of tension.
This property is known as plasticity.
Plasticity makes it impossible to correlate muscle length with tension and to identify resting tension in smooth muscle.
A good example of this occurs in the bladder. As the bladder fills and becomes distended, the intravesical pressure does not initially rise because of the plasticity of the smooth muscle in the bladder wall. Eventually, as the muscle and connective tissue become more stretched, compliance falls and pressure does rise. Additionally, forceful muscle contraction is stimulated by stretch, causing pressure to rise steeply.
Describe the spontaneous activity of the smooth muscle
Visceral smooth muscle has an unstable membrane potential. Because of this instability, it is not really a resting potential. With an average value of -50 mV, the membrane potential tends to be lower when the tissue is active, and higher when it is relatively inactive (Fig 1).
Action potentials develop spontaneously from oscillations in the membrane potential. The principle inward current is of calcium ions. The action potential leads to muscle contraction which is independent of nerve supply.
Because of the gap junctions connecting visceral smooth muscle cells, action potentials spread throughout an area of smooth muscle. This is the syncytial function.
There are also groups of cells which exhibit pacemaker potentials and act as pacemakers, as in the heart. However, in smooth muscle these pacemakers occur in multiple foci which shift from place to place.
Describe the parasympathetic tone in the GI tract
In the gastrointestinal tract the effect of parasympathetic tone is to increase motility, relax sphincters and increase secretion.
Acetylcholine is released from parasympathetic nerve endings and binds to M3 muscarinic receptors. These are G protein-coupled, acting via phospholipase C activation and inositol triphosphate (IP3) production to increase intracellular calcium.
Describe sympathetic tone
Sympathetic tone has the opposite effect to parasympathetic tone. It is mediated via alpha and beta receptors.
Alpha receptors activate phospholipase C using IP3 and diacylglycerol as second messengers.
Beta receptors act via G proteins to stimulate adenyl cyclase and produce cyclic adenosine monophosphate (cAMP) as a second messenger.
Both of these processes result in a decrease in free intracellular calcium and reduced muscle fibre contraction.
Multiunit smooth muscle function:
Multiunit smooth muscle cells are non syncytial, i.e. they do not have gap junctions. Because of this, action potentials and contractions do not spread to other muscle fibres as they would do in visceral smooth muscle.
Action potentials in multiunit smooth muscle do not tend to occur spontaneously, so contraction is controlled by the autonomic nervous system and humoral factors such as epinephrine or histamine.
However, multiunit smooth muscle fibres each have individual nerve endings, an arrangement which is similar to striped muscle. This enables the contractions of multiunit smooth muscle to be finely controlled and well localized, in contrast to the widespread coarser contractions in visceral smooth muscle. An example of multiunit smooth muscle where this fine control is particularly appropriate is the iris of the eye.
What effect does nitric oxide have on vascular smooth muscle?
Among its many functions, nitric oxide (NO) has an important role in the relaxation of vascular smooth muscle (Fig 1).
NO is produced in the endothelium by nitric oxide synthase (NOS), which is activated by an increase in endothelial intracellular calcium. This increase occurs in response to a number of stimuli, including agonists such as acetylcholine and mechanical stretch.
NO then diffuses into adjacent vascular smooth muscle, where it activates guanylyl cyclase (GC) to catalyse the formation of cyclic guanosine monophosphate (cGMP) from guanosine triphosphate (GTP).
cGMP activates protein kinases leading to a fall in smooth muscle intracellular calcium and muscle relaxation.
