has actin and myosin, but lacks organized sarcomeric structure
organized in:
contractile filament domains: contains actin and myosin organized into thin and thick filaments
dense bodies: composed of
a -actinin (major protein of Z-line), and act to anchor the thin filaments
intermediate filament domains: desmin and vimentin which attach intercellular dense bodies to the memb dense bodies
individual cells can shorten 70% of their resting length (cardiac shortens 1.8-1.6, 10%)
thin/thick filament interaction is "plastic" (important for constrict/dilation of blood vessels)
Actomyosin ATPase –
actomyosin ATPase of smooth muscle (SM) is the same as striated muscle
Regulation
regulated by thick filament instead of thin filament as seen in cardiac and striated muscle
As an ATPase, SM myosin is "off" and must be activated by phosphorylation of MLC20
Also causes a conformational change (10S to 6S) in the myosin molec
SM is also regulated by Ca++
Ca++ binds to Calmodulin and this complex binds to and activates MLCK which in turn phosphorylates MLC20 and enables myosin to interact with actin and force develops
MLC phosphatase dephosphorylates MLC20
Electromechanical Coupling
A/P
Þ opening of voltage sensitive Ca channels (L-type) Þ Ca influx Þ Ca binds to calmodulin and this complex activates MLCK Þ contraction
Pharmacomechanical Coupling
SM can also contract without a change in memb potent.
Agonist binds to its receptor (
a , AII, ET, ACh) and activates a G-protein which activates phospholipase C which hydrolyzes PIP2 into IP3 and DAG
IP3 binds to a receptor on the SR which releases Ca
Þ Þ Þ contraction
Smooth Muscle Relaxation
NO relaxes SM via the production of cGMP
Stimulation of
b 2-receptors also relaxes SM
Stimulate
b 2-receptor Þ activation of adenlyate cyclase Þ converts ATP to cAMP Þ PKA which inactivates MLCK Þ relaxation
Phosphodiesterase inhibitors (milirone and amrinone) prohibit cAMP
Þ AMP thus causes a relative increase in cAMP Þ relaxation Þ ß in peripheral vascular resistance because radius increases
treats pulmonary diseases, chronic obstructive pulmonary disease (COPD) and asthma
Smooth Muscle Contraction
agonist induced Ca sensitization
: at similar Ca conc., force is higher for agonist stimulation than for memb depolarization
why? G-protein
Þ decreased MLC phosphatase activity Þ increased phosphorylation of MLC Þ "extra" force
Force Maintenance
As tone
ß in arterial SM, BP falls and flow to an organ Ý
As tone
Ý , BP Ý and flow to an organ ß
Force maintenance:
for SM contraction, Ca, MLC phosph, and force all Ý ; but, Ý in Ca and MLC Phosph is transient, while force is maintained after this fall in MLC phosph
At this time, SM is resistant to fatigue and the rate of ATP hydrolysis falls to low levels
Relaxation and Restoring Forces
there is no antagonist for SM; once it shortens, it must re-lengthen
re-lengthening takes place in single cells, how?
Intermediate filaments compressed during contraction generate restoring forces in SM (similar to a spring)
Force vs Length Relationship
similar to striated musc, due to overlap of thin/thick filaments, SM has an optimal length along with ascending and descending limbs
however, this relationship is "plastic"
if allowed to accommodate to its new length, contract will be the same as that obtained at its optimal length
Force vs Velocity Relationship
hyperbolic; as force increases, velocity decreases and vice versa
SM has an internal load (used for re-lengthening tissue (intermediate filnament domains) after a contract) similar to cardiac muscle which must be overcome in order to contract
Classification of Smooth Muscle
Based on Neuronal Regulation
2 distinct patterns of innervation: multi-unit and single-unit SM
Multi-unit SM (present in vascular system)
Each SM cell is independent
A single nerve fiber will innervate several SM cells and a single cell may have input from more than a single nerve
No A/P are generated in general
Contraction due to internal stores of Ca in SR
Maintains a continuous resting tone, referred to as tonic SM
Single-unit SM (present in GI and GU)
Act synchronously; linked by gap junctions to form an electrical syncitium
Some cells are innervated and others not innervated at all
Nerve muscle junctions often restricted to a small region of cells (pacemaker cells)
Membrane potential is depolarized, A/P propagates thru the tissue and contracts synchronously
Contraction due to transmemb flux of Ca during the A/P
Twitch contractions can be summated to produce a large tetanic contraction