Lecture 2 - Muscle Structure and Function - Part 2 PDF

Skeletal muscle and motor unit structure and function Michael Paris School of Kinesiology and Health Science York University, Toronto, ON Santiago Ramón y Cajal 1852 - 1934 ‘Parent’ of neuroscience/ neurobiology/neuroanatomy Nobel prize 1906 The Motoneuron Soma (cell body) – ventral portion of gray...

Skeletal muscle and motor unit structure and function Michael Paris School of Kinesiology and Health Science York University, Toronto, ON Santiago Ramón y Cajal 1852 - 1934 ‘Parent’ of neuroscience/ neurobiology/neuroanatomy Nobel prize 1906 The Motoneuron Soma (cell body) – ventral portion of gray matter in SC. >100/muscle (muscle dependent) Post-mitotic after birth – loss with aging and disease Soma (alpha) extrafusal fibres (gamma) intrafusal fibres Small soma supports many long processes (eg. L 4,5 motoneurones) Synapse: Electrical or chemical junction between neural tissues. Site of information control Single motor neuron branches at terminal end to innervate multiple muscle fibres (more on this later) Key factors regarding membrane potential: ✓ It is a separation of charge across a membrane Leak channel (Na and K) ✓ Difference in the relative number/concentration of cations (+ ions) and anions (- ions) in the intracellular fluid (ICF) and extracellular fluid (ECF) ✓ Electrochemical gradients determine net movement of ions across membrane ✓ Difference in permeability of key ions ✓ Leak channels ✓ Gradient maintained with Na-K ATPase pump Changes in membrane potential alter the permeability of voltage sensitive ion channels – basis of action potential ECF ICF Voltage-sensitive Na and K ion channels open when a sufficient membrane voltage is reached (known as threshold voltage) – initiating signal for the action potential! Action potential = changes in membrane potential due to opening and closing of Na and K voltage sensitive channels Action Potential Action Potential Disturbance of the resting membrane pot. (electrical, chemical or mechanical) can cause an action potential in nerve, or muscle tissue. Selective permeability to ionic movements of mainly Na+ and K+ Membrane pot. Na+ conductance K+ conductance Normal resting membrane pot. = ~ -70mV. If threshold is reached a rapid change in ionic conc. causes a reversal of the membrane pot. to positive (~ +30 to +50mV). (Spike potential) Net charge of excit. & inhibit. synaptic pots. (MN ~10K synapses) generates an AP at the axon hillock if critical threshold is reached. (Excit. > Inhib.) Synaptic pots. All-or-none potential self-propagating AP amplitude is invariant. Neural info. is encoded by the freq. and pattern of impulses (rate coding) – big take home Refractory periods variable among diff. MN types and determine basic firing rates. Propagation of the action potential Axon hillock – site of action potential initiation high density of voltage Na and K channels Larger diameter axons = faster conduction (lower resistance to flow) Conduction velocity = 45-120m/s Larger diameter nerves = faster propagation Myelination and Saltatory conduction in speed without increase in diameter, reduces metabolic cost. Safety factor for conduction: 5 to 6 = ratio between the amount of current available and the amount required for depolarization Nerve Conduction Velocities Nerve fibre diameter (µm) Specialized Neuromuscular Synapse = Neuromuscular Junction (NMJ) chemical amplification of the axonal AP to depolarize the muscle = site of control Nerve terminal releases Acetyl-Choline into NMJ Acetyl-Choline binds onto its receptor on specialized portion on muscle fibre (motor end plate) Nerve terminal AChR on muscle Combined Motor nerve terminal contains synaptic vesicles of Acetylcholine Acetylecholine (Ach) Acetylcholinesterase NMJ Transmission Action potential reforms in the muscle (also contains voltage-sensitive Na and K channels) Choline is recycled from the NMJ and used to re-synthesize ACh At rest (no AP), there is spontaneous, random movement, or cycling of ACh release and uptake which causes synaptic noise or Miniature EndPlate Potentials (MEPPs) Compare with Excitatory Post-synaptic Potentials (EPPs) which cause muscle depolarization if sufficient Ach post-synpatic receptors are engaged by Ach. **under normal conditions of excitation (activity), axonal or junctional transmission does not seem to be a limiting factor for force generation - large safety factors Excitation-Contraction Coupling (EC coupling) Width of NMJ synaptic space (cleft) is ~ 30nm NMJ time delay ~0.2ms 1. AP propagation into T-T 2. Voltage-sensitive activation of dihydropyridine receptor 1. Physically linked with RYR 3. Ryanodine receptors open on SR 1. releases Ca+2 from SR 4. Ca+2 diffuses to thin filaments 5. Ca+2 activates thin filaments (exposes myosin binding sites) 6. Ca+2 sequestered into SR through sarco-endoplasmic reticulum Ca+2 ATPase pump (SERCA pump) E-C coupling and Ca+2 release Elect. Chem. Mech. action pot. “active state” muscle force response Electrochemical input impulse is filtered by the muscle: muscle transforms the signal and the output is smooth and delayed Big picture concepts: CNS expression requires muscle Muscle tissue and its organization set the limits of speed & power of contraction, and the nervous system controls and coordinates contraction within these limits. These limits are not immutable, and are activity dependent Big Job of Control: - agonists, antagonists, synergists - frequency, intensity, duration of contraction - types of contraction, or tasks - sensory feedback control The nervous system can generate only a stereotyped all-or-none train of stimuli (APs), thus fundamental control of muscle contractions is simplified (to varying degrees) by the nervous system’s exploitation of the unique organizational and functional properties, and plasticity of muscle. You have a great basis to understand NM physiology – the coordination between neural output and muscle responses. We will integrate these at the Motor Unit level … How is the activation signal to the muscle controlled? Stay tuned!