Physiology Unit 2

Muscle Physiology In Physiology Today

• Characteristics – Striated – Multinucleated – Voluntary • Organization – Myofiber • –

• Functional unit of skeletal muscle • Composed of 3 filaments – Thick filament • – Thin filament • • • – Elastic filament • Thick and Thin Filaments of Contraction

• Cross bridges form between the thick and thin filaments • Thin filaments slide across the thick filaments – Thin filaments will move closer together – Distance between Z lines decreases – I band and H bands shorten during contraction – A band stays the same Muscle Physiology

• 2 distinct events happen which lead to 1.Electrical events – – Receptor activation – EPP – AP – Electrical events trigger the mechanical events 2.Mechanical events – Developing tension in the muscle – Increase Ca2+ levels – contractile proteins moving – muscle fiber shortens Stimulus to Contraction

• Stimulus – Receptor activation – Skeletal muscle: ACh binding to N-Achr – Results in an EPP • Latent period – Excitation-Contraction coupling • Contraction period – Cross-Bridge Cycling – Generates tension in the muscle • Relaxation period – Stimulus ends or cell fatigues – Muscle returns to its resting state Muscle Twitch Stimulus

• Somatic motor neurons innervate skeletal muscle • Largest diameter neurons • Myelinated • High velocity AP • Upon reaching muscle, axon divides into many branches • Each branch forming a single junction with a muscle fiber = EPP to AP Action Potential to Contraction

• AP lasts 1-2 ms • Completed before any mechanical activity begins • Mechanical activity (contraction) may last >100 ms • Electrical activity (action potential) does not act on contractile proteins • Produces a state of increased cytolsolic [Ca2+] – Resting [Ca2+] = 0.1 mMol/L – After AP [Ca2+] = 1 mMol/L Latent Period

• Excitation-Contraction Coupling • Sequence of events from the generation of an AP across the to Ca2+ release inside of the myofiber • Sarcolemma is an excitable membrane – Generating an AP (from EPP) – Propagating an AP – Similar mechanisms as neurons Contraction Period

• Increase in intracellular Ca2+ levels trigger the mechanical events • Ca2+ activates Cross- Bridge Cycling

• Lateral sacs store Ca2+ • T-tubule has DHP receptors – DHP receptors are normally voltage gated Ca2+ channels – In skeletal muscle t-tubules, acts as a voltage sensor • SR has ryanodine receptors – Intracellular Ca2+ channels – When Ca2+ channels open, Ca2+ moves into cytoplasm

Calcium Release

• DHP receptors trigger calcium release • Ryanodine calcium channels open • Influx of calcium from SR into cytoplasm • Calcium influx triggers cross bridge cycling Activation by Ca2+ • Tropomyosin covers the myosin binding sites on actin • Troponin holds tropomyosin in place - has 3 sub-units 1. • inhibitory 2. • Tropomyosin binding 3. • Calcium binding • Increase in intracellular Ca2+ levels cause Troponin C to bind to Ca2+ which exposes binding sites on actin Troponin Cross Bridge Cycling

1. Attachment of the myosin cross-bridge to actin of a thin filament 2. Movement of the cross-bridge, pulling on the thin filament – Each cross-bridge moves independently of all other cross- bridges – Asynchronous pulling action 3. Detachment of cross-bridge from the thin filament 4. Energizing the cross-bridge so it can again attach to a thin filament and repeat the cycle Cross-Bridge Cycling ATP in Muscle Metabolism

Uses of ATP in Muscle Muscle Contraction Requires Contraction A Lot of ATP!

• Activation of myosin • No ATP “storage” – High-energy myosin • 3 pathways for • Release of myosin head regeneration from actin molecule – Phosphagen system • Active transport of Ca2+ – Glycolysis into SR from the – Aerobic respiration

+ ATP + H20 à ADP + pi + H + Energy Sources of ATP

1. Phosphagen System 2. Glycolysis 3. Oxidative phosphorylation Phosphagen System

• Creatine – Natural produced ny the body – Made from amino acids • Creatine Phosphate – A store of high energy phosphate • Creatine Kinase – Transfers phosphate group from CP to ADP – Present at 3x higher concentration in skeletal muscle CrP + ADP + H+ ----> Cr + ATP Phosphagen System

• Adenylate Kinase – A way to quickly make ATP – ADP + ADP ---- > ATP + AMP Aerobic Respiration

• Primary source of ATP production for muscle during rest or light exercise • Fuel utilization by skeletal muscle – fatty acids – muscle glycogen – blood borne glucose Anaerobic Mechanisms

• Oxygen consumption – Exercising muscle can consume more ATP than can be produced by aerobic respiration – Muscle cells will utilize available glucose and glycogen reserves – Glycolysis will then produce ATP to keep up with the demand of the active muscle • Lactic acid accumulates – Oxygen Debt • The amount of oxygen consumed to get the muscle cells and plasma back to normal conditions – Glucose levels – Glycogen reserves – Converting lactic acid back to pyruvic acid

• single cells, no striations • circular layer arrangement • no or troponin • actin:myosin ratio = 13:1 • utilizes Ca2+/ mechanism • graded depolarizations • single unit vs multi-unit • autonomic innervation Smooth Muscle