Contraction and excitation of smooth muscle Smaller fibers Principle of contraction Same as skeletal muscle in many aspects Attraction between myosin and actin Different arrangement of muscle fibers

Types of smooth muscle Different among different organs Two types Physical dimensions Organization (bundle/sheet) Responsiveness to different stimuli Innervation Function Two types Multi-unit Unitary (single-unit)

Multi-unit smooth muscle Composed of discrete muscle fibers Innervated by a single nerve ending Covered with basement membrane Separation of individual fiber Independent contraction Controlled by nerve signal No spontaneous contraction

Unitary/single-unit smooth muscle Mass of muscle cells contracting as one unit (syncytical smooth muscle) Aggregated into sheet or bundle Adhered together Membrane (force) Gap junctions (action potential) Critical for contraction Found in the wall of digestive, urinary, and reproductive tracts, and blood vessel

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Contractile process Chemical basis Actin and myosin filaments No troponin complex Interaction of filaments Similar to that of skeletal muscle Activated by Ca ions Require ATP

Contractile process Physical basis No stratiation Actin filaments Attached to dense bodies Myosin filaments Interspersed among actin filaments Ratio of actin filaments to myosin filaments More actin in smooth muscle Greater ratio of fiber length

Individual contractile unit Large number of actin filaments (attached to two dense bodies) Single myosin fiber (half-way between two dense bodies) Dense body (Z-disc) No regularity Side-polar arrangement of myosin cross-bridges

Individual contractile unit Side-polar arrangement of myosin cross-bridges One side of myosin heads pull actin fiber in one direction Greater contraction (80 % of the length)

Smooth muscle contraction Comparison with skeletal muscle Prolonged tonic contraction Different chemical characteristics

Smooth muscle contraction Cycling of myosin cross-bridge Slower repeated attachment and release of actin by cross-bridge (1/10 to 1/300 of skeletal muscles) Increased time of interaction Lower concentrations of ATPase in the cross-bridge heads

Smooth muscle contraction Energy requirements Much less (1/10 to 1/300) compared to skeletal muscles Slow attachment and detachment of myosin heads Critical for energy conservation Indefinite contraction of visceral smooth muscles

Smooth muscle contraction Slower onset of contraction and relaxation Typical smooth muscle Contraction initiated 50 to 100 mSec after excitation Full contraction achieved 0.5 sec later Decline in contractile force 1 to 2 sec Total time for process 1 to 3 sec

Smooth muscle contraction Slower onset of contraction and relaxation 30 times slower than skeletal muscles Various type of smooth muscles Slower detachment and attachment of cross-bridges Slower response to elevation in Ca concentrations

Prolonged holding of contraction Force of contraction Greater maximum force of contraction 4 to 6 kg/cm2 compared to 3 to 4 kg/cm2 for skeletal muscles Prolonged attachment of myosin to actin Prolonged holding of contraction Latch mechanism Low energy consumption Continuous stimulation

Stress-relaxation Ability to return to near the original force of contraction shortly after elongation or contraction Increased stretching of hollow organ Immediate rise in pressure Pressure returns to normal even when the organ is continuously stretched

Reverse stress-relaxation Sudden decrease in pressure Immediate decrease in pressure Pressure returns to normal immediately after the decrease in size

Increase in size Increase in pressure Normal size Normal pressure Decreased size Normal pressure Increased size Normal pressure Decrease in size Decrease in pressure

Role of Ca ion Initiating factor Increase in intracellular Ca Rise in intracellular Ca Increase in intracellular Ca Nerve impulses Hormones Physical External environment

Role of Ca ion No tropinins Different mechanisms

Role of Ca ion Calmodulin as a regulatory protein Binds Ca Activation of myosin kinase by Ca-calmodulin complex Phosphorylation of myosin light chain Regulatory chain within the mysoin head Interaction of myosin head with actin filament

Cessation of contraction Loss of Ca Myosin head must be dephosphorylated Myosin phosphatase Timing of cessation and relaxation Myosin phosphatase concentration dependent

Source of Ca ions Less-developed SR compared to skeletal muscle Influx of Ca ions fromextracellular fluid Concentration gradient (<10-7 M inside vs. > 10-3 M outside) Needs 200 to 300 mSec for diffusion (latent period) Contraction of smooth muscle is highly dependent on extracellular Ca

Role of SR Sacroplasmic tubules in some large smooth muscle cells Caveole (invagination of the membrane) Rudimentary analog of T-tubules Stimulates release of Ca by sacroplasmic tubules when the action potential reaches More extensive the sacroplasmic reticulum, rapid contraction of muscle

Removal of Ca Relaxation of smooth muscle Ca pump Move Ca from the inside to the outside or into sacroplasmic tubules/reticulum Slow-acting (longer contraction)

Regulation of latch phenomenon Mechanism Myosin kinase and myosin phosphatase Activation of both enzymes Increased velocity of contraction (increased cycle frequency) Inactivation of enzymes Decrease velocity of contraction Increased interaction between myosin head and actin filament (per cycle) Increased number of myosin heads interacting with actin filament (increased static force of contraction)

Nervous and hormonal control Skeletal muscle Exclusives stimulated by nerve fiber Smooth muscle Contains receptors for various stimuli Stimulatory Inhibitory

Neural stimulation Neuromusclular junction Innervated by autonomic nerve fibers Only on the top layer Excitation potentials travel toward the inner layer by action potential conduction or additional diffusion of neurotransmitter Nerve fibers branch diffusely on top of sheet No direct contact Diffusion junction (few nm to few mm away from muscle membrane)

Formation of varicosities No motor end plate Vesicles containing neurotransmitters Acetylcholine Norepinephrine Formation of contact junction Close proximity of varicosities to the muscle membrane (20-30 nm) Faster contraction compared to diffusion junction

Release of excitatory and inhibitory substances Acetylcholine Norepinephrine Secreted by different fibers (either/or, not both from the same fiber)

Acetylcholine Norepinephrine Excitatory in some muscles Inhibitory in other muscles Norepinephrine Excitatory in muscles where acetylcholine is an inhibitor Inhibitory in muscles where acetylcholine is a positive stimulator

Differential responses to acetylcholine and norepinephrine Types of receptors

Membrane and action potential Membrane potential -50 to -16 mV at resting state Action potential Similar to skeletal muscle in unitary smooth muscle Absent in multi-unit smooth muscles

Action potential in unitary smooth muscle Spike potential Action potential with plateau Initiated by factors other than neural signals

Spike potential Same as the action potential in skeletal muscle 10 to 50 mSec in duration

Action potential with plateaus Delayed depolarization As much as 1 second Prolonged contraction of the muscle

Role of Ca channels Numerous voltage-gated Ca channels Few voltage-gated Na channels Action potential generated by the influx of Ca ions Ca channels open slower than Na channels and remain open longer Prolonged plateaus Ca ions more critical for smooth muscle contraction

Slow wave potential Self-excitation of some smooth muscles Absence of stimuli Slow wave potential Slow wave (pacemaker wave) Not action potential (no spreading) Localized phenomenon

Cause of slow wave Importance Unknown Initiation of action potential One or more action potential per each peak of slow wave Rhythmical contraction of smooth muscle Initiation of action potential by stretching

Depolarization of multi-unit smooth muscle Contraction of multi-unit smooth muscle Input from autonomic nerve fiber Binding of neurotransmitters to their receptors Depolarization No action potential Nerve fibers are too small to initiate action potential Junctional potential (local depolarization) Electronic transmission to other muscle fibers

Role of tissue factors and hormones Non-nervous factors Do not generate action potential Local tissue factors (often associated with smooth muscle surrounding blood vessels) Oxygen Carbon dioxide Hydrogen ions

Hormones Requires presence of excitatory/inhibitory receptors Mechanisms Changes in membrane potentials Release of Ca ions from SR Removal of Ca ions Alteration of enzyme activity