BISC 307L 1st Edition Lecture 11 Current Lecture Excitation Contraction Coupling o The neuromuscular junction o Picture Given that there is an AP in the muscle fiber spreading down the sarcolemma plasma membrane in the muscle Mechanism of the action potential is the same as an unmyelinated axon What happens is 1 T tubules invaginations of the plasma membrane which are transversally oriented and spaced one per sarcomere Extends in a ring around the myofibril 2 Smooth ER blue flat sac of membrane arranged in a belt along each myofibril Flanking the SR is this sac o The AP spreads through the T tubule How much depolarizes a lot because there are high density of Na channels so whole T tubule system gets depolarized o Connections between the T tubule and the SR Blue membrane t tubule membrane Yellow membrane SR membrane The membrane potential exists across the T tubules membrane for restin condition 2 complexes of proteins 1 Dihydropyridine receptor t tubule voltage sensing protein not a channel but the membrane it sits in is depolarized 2 Ca2 channel pump Ryanodine receptor takes Ca2 out of the cytoplasm and pumped into the SR lumen lowers concentration of Ca2 inside the cell so that there is no contractions at resting Ca2 released from SR when the Ca2 channel opens which will trigger contractions After t tubule membrane is depolarized causes conformational change in dihydropyridine receptor which is connected to the Ca2 channels dotted lines and when these links pull calcium channel opens mechanically gated but voltage dependent Contraction continues until Ca2 sequestered again into the SR by the pumps The total capacitance of a muscle fiber is way higher than that of an axon membrane is bigger because of internal membranes in muscle fiber How Ca2 triggers contraction o Relaxed 10 8 M Ca2 Thick filament at top with myosin head Tropomyosin lies along the helix of actin Troponin is a complex of four proteins and one is a Ca2 binding protein At this Ca2 concentration the Ca2 is not bound to most of the tropoinin and thus tropomyosin is bound to binding site for myosin head for actin meaning the muscle is relaxed cant bind o Cycling 10 7M Ca2 When calcium rises 10 fold that s enough to bind to troponin which will cause a conformational change moving tropomyosin aside so myosin can bind to actin binding site and cross bridges can occur and the filaments will slide until Ca2 resequestered Muscles are characterized by how fast they are ATP hydrolysis step is the rate determining step The fall off of force is determined by how fast Ca2 can be resequestered determined by the number of pumps in the SR Force Length Relationship o Experiment Fix muscle at various lengths measure force produced Whole organ level Record how the muscle behaves Depolarize it by passing current through Muscles generate force and they shorten Lifting something heaving not moving it generating force but constant length Called a isometric recording Fix muscle at some length As you stretch it more and more the force is going to fall off This relationship is a function of the overlap between the thick and thin filaments maximal force is attained at length Lo when you have the optimal overlap between thick and thin filaments Stretching it more will lessen the maximal overlap between the filaments Muscles add sarcomeres as they grow Force Velocity Relationship o Experiment Apply a fixed load to the muscle measure rate of change in length Harder to measure Free to shorten Shorten as fast as it is going to shorten Add to muscle at the same instant that you stimulate it Measuring the speed for which it shortens Positive velocity is shortening Negative velocity is lengthening Load is the external force applied Called isotonic recording constant tension When load is minimal there is the fastest velocity of shortening Reaches zero velocity if you add enough load maximum force the muscle can generate no shortening or lengthening If increase external force more the muscle will contract but it actually will lengthen negative velocity of shortening If increased enough the muscle collapses catastrophically When a muscle is active and it shortens it is called a CONCENTRIC contraction like lifting a small weight When catching a water balloon you cushion is so the muscle is acting like a spring When it lengthens as it contracts called a ECCENTRIC contraction Properties Used to Classify Muscle Fibers o 1 Whether ion channels in sarcolemma allow action potentials all or none twitch or not graded or tonic contractions enough voltage gated ion channels There may not be enough Na channels in the membrane not as dense There may be enough for active local graded potentials but not a full all or none o 2 Rate of cross bridge detachment during contraction related to ATPase activity of myosin isoform Determines Vo Rate determining step hydrolysis of ATP Vo is the maximum velocity of shortening o 3 Number of Ca2 pumps in the SR determines rate of relaxation 2 and 3 together determine twitch duration o 4 Number of mitochondria and capillary density which determines capacity for oxidative phosphorylation and fatigue resistance how long can the fiber keep up activity determines muscles capacity for oxidation Motor Units o Lumped muscle fibers into three categories 1 Type 2B FF fast fatigue able more numbers of fibers 2 Type 2A FR Fast fatigue resistant 3 Type 1 SR slow fatigue resistant slower motor neurons muscle fibers smaller generate less force o The minimal contraction is the activation of a single motor unit At top is the AP in the motor neuron