Medicine Notes Physiology and Pharmacology Notes
1st year Oxford notes and tutorial essays on Physiology and Pharmacology...
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Smooth muscle
Unlike cardiac and skeletal muscles, smooth muscle cells typically maintain continuous, relatively low-energy contractions, which can be modulated and co-ordinated to produce rhythmic or wave-like contractions throughout a tissue.
The strength of contraction can be controlled by the autonomic nervous system, hormones and local metabolites. In a few cases, the autonomic nervous system directly controls contraction (eg., in the iris), but more usually it merely modulates spontaneous contractions in the muscle.
In some muscles (eg., the respiratory tract), there is no autonomic innervation
-non striated muscle- responsible for contraction of hollow organs
Walls of the blood vessels
Respiratory system
Gastrointestinal tract
Urinary tract- ureters,bladder, urethra
Reproductive tracts
Piloerector muscles associated with hairs in the skin
Iris of the eye
Structure –difference between skeletal and cardiac non striated
Contractile machinery
-smooth muscle thin filament is longer than in cardiac muscle allowing greater shortening
-Lacks troponin, cardiac calcium sensitive regulatory protein, replaced by proteins caldesmon and calponin on vascular smooth muscle thin filaments
-myosin differs from the heart and participates in contraction when phosphorylated
-actin filaments are rooted in dense bands on the inner cell membrane and dense bodies in cytoplasm. Alpha actinin. Dense bodies are not aligned so lacks the striated appearance of cardiac and skeletal muscle
-intermediate filament- ctyoskeletal element links dense bodies and dense bands- so the cell contracts as a whole- proteins desmin and vitamin
SR
-Sarcoplasmic reticulum, releaseable store of calcium but poorly developed in smooth muscle, calcium store is not very big
-In order to maintain tonic contraction, extracellular influx if required- so calcium channel blockers such as nifidipine are good resistance vessel dilators
-The SR is close to the sarcolemma so facilitates store release by agonists such as noradrenaline- IP3 binds to IP3 receptors
-Calcium release channel- ryanodine receptors- basal state- ryanodine receptors spontaneously release brief bursts of calcium called calcium sparks- raises the calcium concentrations locally in the subsarcolemmal region- activates nearby calcium dependent K channels- hyperpolarisation- so spark no contraction
Gap junctions
-vascular myocytes are connected to each other by homocellular gap junctions- made up of protein connexins- 6 connexins- make hemi tube- connexon- the connexons in adjacent cells join end to end to connect the cytoplasm of the cells
Caveolae
-cell surface highly invaginated- increase the total surface area of the membrane
-cytoplasmic surface has a striated coat of protein- caveolin 1, caveolar membrane is enriched in cholesterol, sphingomyelin
-they contain high concentrations of B adrenergic receptors, G proteins, L type calcium channels, K atp channels
Types of smooth muscle
-Visceral/ unitary smooth muscle
Large sheets of cells with common innervation connected by gap junctions which function as low resistance electrical connections and permit coordinated contraction
Found in walls of hollow visceral organs- gastrointestinal tract,uterus,, blood vessels, airways
Spontaneous contractions can oocur- stretch increases tone
Contractions are mostly due to circulating hormones but can be modulated by nervous stimuli
There can be enpassant junctions on a few cells and the excitation spreads to other cells
Multi-unit smooth muscle
Fibres receive individual innervations and act independently- multiunit smooth muscles are capable of finer control- found in the iris, cilary body of the eye, piloerector muscles of the skin
Spontaneous contractions don’t occur
Contractions mostly caused by nervous triggers and is modulated by hormones
Functions more like those of skeletal muscle
Exciation
Neurogenic
-Smooth muscle receives synaptic input from the nervous system-neurons are part of the autonomic nervous system, neurons make multiple contacts with the smooth muscle cell- at each point the axon diameter expands to form a sweries of swellings called varicosities- these contain presynaptic components for vesicular release
-each varicosity is close to the post synaptic membrane but there is little specialisation of the post synaptic membrane
-Parasympathetic –release ACH- act on M3, bronchial smooth muscle, GI tract, bladder
-contraction is initated by 2nd messengers and not changes in Em
-Multiunit smooth muscle: each smooth muscle receives synaptic input
-visceral smooth muscle: many gap junctions- common innervations- relies on the formation of action potentials- flux of calcium through the gap junctions
-Some smooth muscle are electrically excitable and driven entirely through nervous activity- vasdeferens and arterioles- arterioles are tonically constricted due to the basal release of Noradrenaline from sympathetic vasoconstrictor nerves-bind to alpha 1 adrenergic receptors
-sympathetic nervous activity can either cause contraction- alpha adrenergic receptors- contraction of iris, beta adrenergic stimulate relaxation- vas deferens, arterioles, cilary muscles
Myogenic : Spontaneous electrical activity modulated by nervous activity
i) Tonic contractions: visceral smooth muscle has an unstable membrane potential, voltage gated calcium channels are active at resting Em, depolarise cell enough to activate more voltage gated calcium channels. Increase in Calcium activates Ca dependent potassium channels-porgressive hyperpolarisation and termination of depolarisation
ii) Phasic contractions: GI tract: Generation of slow waves due to interstitial cells of cajal which are coupled to smooth muscles cells via gap junctions. In these cells there is a cyclic increase and decrease in the rate at which Na ions are pumped out of the membrane-when Na+ pumping increases-membrane potential becomes more negative, when pumping decreases Em increases- cyclic variations of Em, peak...
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1st year Oxford notes and tutorial essays on Physiology and Pharmacology...
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