Lecture 16 – Motor Pathways II Flashcards
Action Potential vs. Contraction:
muscle spindles
- myotactic reflexes
- gamma motor neurones
- molecular mechanisms – actin and myosin causes contractions by releasing calcium via intracellular spores
- muscle contraction happens over a much slower time scale
- contraction occurs after the action potential has finished
- calcium release happens after the action potential
- reuptake is slow and starts when calcium is released
Twitch and Tetanus:
¥ single AP twitch
¥ summation & unfused tetanus with increased rate
¥ higher rates fused tetanus
¥ twitches emerge and force of contraction gets bigger
¥ maintain the contractions
¥ at high frequencies there’s a smooth emerging of contractions
¥ tetanus is caused by muscle being contracted and stimulated and NOT by microbial toxins
Henneman’s Size Principle:
- The smallest contractile unit of a muscle is not a muscle fibre, but rather a MOTOR UNIT
- A motor unit is the set of muscle fibres that are controlled by a single motor neuron – not a 1:1 relationship – motor groups
- Different neurons can control different fibres
- The number of fibres in a motor unit can vary considerably and is related to the size of the neuron: the bigger the motor neuron (cell body size), the more muscle fibres it innervates
- Henneman’s size principle states that as a muscle is stimulated to contract by neuron W in the CNS, motor units become recruited in order of size, the smaller units are recruited first (because for a given stimulus by neuron W, motor neuron X will be depolarized more because it is smaller), followed by the intermediate ones (Y) and then the largest motor units
- This means that the force generated by a muscle can be finely controlled by the CNS
- Motor units are recruited in order of size
- At higher levels of stimulation there is higher forces of contraction
- This is a method used to control the nervous system
Diversity of Skeletal Muscle:
- fast-twitch glycolytic
- fast-twitch oxidative
- slow-twitch oxidative
diversity
slow fibres: used for posture maintenance etc. Have myoglobin (red) as oxygen store. Many mitochondria. – heavily expressed in legs and arms and specialised for long periods of contractions which is why they have a lot of myoglobin in them (oxygen store) and are specialised for oxidative metabolism
fast fibres: fast myosin isoform, fast Ca transient (high SR Ca pump). Allows rapid shortening but at high energy cost as ATP hydrolysed quickly – produce a fast calcium signal for fast response by hydrolyse quickly so is a high-energy cost
glycolytic fibres: lactate accumulation & acidosis can limit contraction – don’t use oxidative metabolism as they use glycolysis – produce a very quick response
Duchenne Muscular Dystrophy:
¥ X linked disorder: mutation in the dystrophin gene (about 3600 male births)
¥ Skeletal muscle fibres are not linked to extracellular matrix properly
¥ Excess calcium enters and muscle fibres die
¥ Progressive muscle weakness
¥ Average life expectancy 25-30 years
¥ candidate for gene therapy?
- This diagram shows that although training can switch between the fibre types, a lot of it is genetically pre-determined
Myostatin Deficiencies:
¥ Massive muscle overgrowth
Cardiac Muscle:
Broadly like skeletal muscle
But:
¥ Cells incompletely fused
¥ Joined by intercalated discs into a branched syncytium which allows contractions to spread via action potentials
¥ Discs are specialized structures that bind neighboring cells that have gap junctions between them
¥ Control mechanisms different
¥ Different subtypes of myosin, actin etc.
¥ Action potentials different
¥ Excitation-contraction coupling different
¥ Only found in the heart
¥ Intercalated discs contain desmosomes that anchor the cells together mechanically, and gap junctions which couple them electrically
¥ Different ions play different roles – calcium is the strongest
¥ Cardiac muscle has to have a good supply of oxygen and sufficient use of ATP to keep a person alive
Cardiac Muscle Action Potentials:
the action potential can last 200ms
- the brief upspike is due to sodium channels opening
- the plateau part is when the calcium channels become open
- repolarisation is when the sodium channels turn off and the potassium channels open
- there is a bigger role for calcium opening the channels and introducing the action potential
- calcium acts as a voltage sensor
Cardiac Excitation Contraction Coupling:
calcium induced and calcium release is that in cardiac muscle calcium has to enter from the outside which is taken in and brings about a contraction
- the trigger for actin-myosin cross link formation is an increase in cytoplasmic calcium and this calcium comes largely (80%) from the sarcoplasmic reticulum
- However, the mechanism by which this calcium is released from the SR is rather different from that in skeletal muscle
- Remember that in skeletal muscle the DHP receptor (L type calcium channel) acts as a voltage sensor and is mechanically coupled to the ryanodine receptor on the SR
- No calcium needs to enter via the DHP receptor in order for SR calcium to be released by the ryanodine receptor in skeletal muscle
- In cardiac muscle, L type calcium channels are also involved
- However, they do not appear to be mechanically coupled to the RyR – instead, opening of the RyR is triggered by calcium that enters via the L type channels - known as Calcium Induced Calcium Release (CICR)
- Some (20%) of the rise in cytoplasmic calcium that triggers cross bridge formation is due to direct entry via the L type channels
Initiation of Contraction - SA node AP:
- In skeletal muscle, contraction is first signaled by an upper motor neuron in the CNS
- This makes a synapse with a lower motor neuron in the spinal cord and the axons of the LMN in turn synapse with the skeletal muscle
- Acetylcholine is released at the NMJ by the LMN and triggers an action potential in the muscle membrane. In cardiac muscle, contraction is said to be MYOGENIC i.e. originates from within muscle itself.
- Myogenic contraction occurs because a specialised group of heart muscle cells in an area called the sinoatrial node are able to generate PACEMAKER POTENTIALS (4 in the diagram). The pacemaker potential is a spontaneous depolarisation of the membrane that causes SA node cells to fire of action potentials at a regular rate – usually 60-100 beats per minutes. The channel that carries the pacemaker current is a nonspecific cation channel called HCN. It has strange characteristics that have also led to this current being called If (I indicates current, f indicates “funny”), when you reach the threshold you get a spike which is the sodium and calcium being carried
- Once an action potential is initiated in the SA node, it spreads down through the cardiac conducting tissue and then into the muscle of the atria and ventricles. The electrical coupling of the cardiac muscle cells (the syncytium) ensures that electrical excitation spreads rapidly
- Under control of the sympathetic and parasympathetic nervous systems
Controlling Contraction:
¥ Force of contraction determined by:
Ð degree of stretch of cardiac muscle (Starling’s Law of the Heart), more the heart is stretched the harder it contracts
Ð concentration of cytoplasmic Ca2+ - can be trigger by autonomic nervous system
¥ this can be modulated by the autonomic nervous system: sympathetic – increase; parasympathetic – decrease.
- Action potentials in the heart are stimulated by heart muscle as it is myogenic
Cardiac Muscle Energy Metabolism:
¥ Heart needs to beat continuously so can’t use glycolytic ATP production – heart cannot choose, must use oxidative
¥ Uses oxidative metabolism
¥ Cardiac muscle needs a good blood supply
¥ Deprivation of blood (O2) supply -> angina, heart attack
Smooth Muscle:
Histologically distinct from skeletal and cardiac muscle
¥ No striations
¥ No t-tubules
¥ Small, spindle-shaped cells
Cells often electrically coupled by gap junctions (“unitary” – acts as syncytium) but can be
Found around hollow organs:
¥ - tubes going through them Ð blood vessels Ð gut Ð bladder Ð uterus Ð bronchi
