Synapse, Excitation-Contraction Coupling
Suggested Reading: Guyton Chapter 7
Pre-synaptic Terminal:Separated from the post-synaptic terminal by a synaptic cleft. The terminal has two internal structures important to the excitatory or inhibitory functions of the synapse; the transmitter vesicles and the mitochondria. When an action potential spreads over a pre-synaptic terminal it lets in Calcium and then it releases the transmitter molecules into the synaptic cleft.
Synaptic Cleft or Trough: The space between the pre-synaptic terminal and the post-synaptic terminal (muscle fiber membrane). The transmitter molecules travel through this cleft to reach the post synaptic membrane.
Post Synaptic Membrane: Separated from the pre-synaptic terminal by the synaptic cleft. Receives the transmitter molecules from the pre-synaptic terminal and opens its channels to allow in small positively charged ions into the cell thus depolarizing the cell.
Synaptic Vesicle: Vesicles that have a high concentration of a molecule that can be used for a transmitter molecule (usually acetylcholine). After the Calcium enters the pre-synaptic terminal, they attach to the vesicles and "encourage" them to bind (fuse) to the pre-synaptic wall thus becoming part of the membrane. The vesicles invaginate and spew its transmitter molecules into the synaptic cleft.
Neurotransmitters: The transmitter molecules that are spewed from the synaptic vesicles into the synaptic cleft.
Exocytosis: The emptying of the synaptic vesicle’s acetylcholine into the synaptic cleft.
Excitatory Post-Synaptic and Post-Synaptic Inhibition: The transmitter molecules bind with a receptor protein. Some of these receptors are excitatory whereas some are inhibitory. So depending on which receptor protein is in the muscle depends on whether the post-synaptic side is excited or inhibited.
Synaptic Receptors: The protein channels that receive the transmitter molecules, which tell them to open the "gate" to the channel.
Transverse Tubules: They are very small and run transverse to the myofibrils. They begin at the cell membrane and penetrate all the way from one side of the muscle fiber t the opposite side. They are full of Extra-Cellular-Fluid.
Sarcoplasmic Reticulum: An extensive endoplasmic reticulum, in the muscle fiber. They hold about 10,000 X’s more calcium than the intracellular fluid.
Intracellular Calcium Concentration: Less than 10 to the –7th molar. Too little of a concentration to elicit contraction.
Active State: When a depolarization hits the Sarcoplasmic Reticulum (SR), Ca++ channels open and large amounts of Ca++ pour down their concentration gradients from the SR into the ICF near the contractile elements. The muscle is now in its active state.
Describe the functional anatomy of a typical synapse, including the following structures: pre-synaptic terminal, synaptic vesicles, synaptic cleft, post-synaptic membrane:The pre-synaptic terminal has a non-excitatory membrane. It contains synaptic vesicles that hold transmitter molecules in very high concentration. The area that separates the pre and post synaptic areas is called the synaptic cleft (or trough). The post-synaptic membrane is on the other side of the synaptic cleft, across from the pre-synaptic terminal. The post-synaptic membrane contains gated protein channels with synaptic receptors that are waiting for the transmitter molecules.
Identify the general patterns of synaptic transmitter synthesis, release, and action at post-synaptic membranes: Acetylcholine is synthesized in the cytosol of the terminal nerve fibers and is then transported through the membranes of the vesicles to their interior where it is stored in a highly concentrated form (about 10,000 molecules of acetylcholine in each vesicle.) When an action potential arrives at the nerve terminal, it opens many calcium channels in the membrane of the terminal. The calcium helps fuse the synaptic vesicles with the terminal wall. As each vesicle fuses, its outer surface ruptures through the cell membrane, thus causing exocytosis of acetylcholine into the synaptic cleft. The acetylcholine binds with the synaptic receptors thus opening the gated channels. The acetylcholine is then split by acetylcholinesterase into acetate ion and choline. The choline is actively reabsorbed into the neural terminal to be reused in forming new acetylcholine. Guyton page 90
Describe in detail the synthesis, release, action, and breakdown of the chemical mediators of cholinergic and adrenergic synapses: See above objective.
Discuss transmission at the myoneural junction and the muscle fiber action potential: Action potential comes down Axon to pre-synaptic terminal. Voltage change opens calcium channels that let Ca++ in that moves the synaptic vesicles to the terminal membrane wall. They fuse with the wall, invaginate and release acetylcholine into the synaptic cleft. Acetylcholine diffuses across the cleft to the receiver protein on the muscle fiber wall and binds with it to open the gate allowing in small positively charged ions which create an action potential within the muscle. This potential causes an increase in the positive direction as much as 50-75 mV...creating a local potential. Only 20-30mV are needed to to initiate the positive feedback effect of Na+ channel activation so there is more than enough depolarization to activate the muscle.
Identify the roles that calcium ions, the transverse tubular system, and the sarcoplasmic reticulum play in excitation-contraction coupling: One of the special features of the sarcoplasmic reticulum is that within its vesicular tubules it contains calcium ions in high concentration, and many of these ions are released when an action potential occurs in the adjacent T-tubule. The action potential of the T tubule causes current flow through the tips of the cisternae that abut the T tubule. At these points, each cisterna projects junctional feet that attach to the membrane of the T tubule. The action potential from the T tubule hitting the sensitive cisternae causes the rapid opening of large numbers of calcium channels through the membranes of the cisternae and their attached longitudinal tubules of the sarcoplasmic reticulum. During this time, the calcium ions responsible for muscle contraction are released into the sarcoplasm surrounding the myofibrils. They diffuse to the adjacent myofibrils, where they bind strongly with Troponin C and the troponin complex undergoes a conformational change that in some way tugs on the Tropomyosin molecule an moves it deeper into the groove between the two actin strands. This "uncovers" the active sites of the actin, thus allowing contraction to proceed. Guyton pages, 78 & 92
Compare and contrast the electrochemical events in skeletal, cardiac, and smooth muscle. How does their physiology relate to their overall role in the body?: Skeletal muscle has a very precise organized internal structure of myosin and actin. It uses the SR to store Ca to be used by the muscle to open the troponin complex, which covers the actin fiber, and this allows the myosin head to bond with the actin and cause muscular contraction. Cardiac muscle looks very similar to skeletal muscle at the molecular level except it has more mitochondria and SR. The differences with cardiac muscle is that skeletal muscle fibers will contract after one action potential per muscle unit of the sarcomere whereas cardiac muscle will contract after one action potential and then the entire cardiac muscle will contract as one sheet of cells all together. Cardiac muscle has one single motor unit versus many, many motor units in skeletal. The other difference with cardiac muscle is that the Ca channels are very slow during the depolarization phase and therefore depolarization will last longer as a plateau before repolarization occurs. Since the Ca channels are open longer more Ca is available and we see a huge single twitch. Smooth muscle is another creature altogether having no organized internal structure. It does have SR and filaments but not set in any particular pattern. Smooth muscle can be divided into Multi-unit and Single unit or Visceral. Multi-unit is small discreet fibers where each fiber is independent and controlled by nerves and synapses. These are found in the eye, in the iris, ciliary, piloerector, and in some larger blood vessels. Visceral is more a whole patch of muscle that works as a single unit. This is found in the gut, uterus and the ureters. They act as a single sheet of cells and fuse together. The fused cells have specialized junctions between them and low resistance pathways. The electrical potentials travel thru entire sheet of cells like cardiac muscle. Smooth muscle cells tend to be very small cells with bunches of dense bodies which can be analogous to the Z lines of the skeletal muscles. They look very random under a microscope. When smooth muscle contracts it also does so in response presence of Ca. This Ca comes from the ECF instead of stored supplies in the SR. This Ca comes through electrically gated channels and engages whatever contractile apparatus in such a way that it activates the cell and allows it to contract. The external cell membranes contain a Ca pump like the SR but this pumps Ca out of the cell into the ECF. The mechanics of contraction are a much slower process than skeletal. This delay is due to Ca having to come a further distance to get where the bond is formed. The electrical event is similar in that there is an action potential but the contraction will be slower and longer in duration. There will be a variable height of the action potential in the smooth muscle whereas skeletal has a fixed height. Smooth muscle lacks the fast Na channels, while they do have the slow Na/Ca channels. Ca is also the predominant ion in smooth muscle contraction but in enters the cell through a slow gated channel and it enters as part of depolarization and for purposes of activating contraction. In visceral smooth muscle there are spontaneous, rhythmic waves of depolarization which occur in cells without any neural input that continue for long periods of time such as peristaltic movements of the gut. There are also hormonal influences on smooth muscle. Norepinephrine and epinephrine will modulate the response of smooth muscle. The other big difference between smooth and skeletal muscle is that skeletal muscle can only shorten to 40% of its resting length while smooth muscle can be stretched out to twice its rest length and can still contract or shortened to ˝ its rest length and still contract. This is r/t its diffuse structure.
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Last Updated 04/10/00 12:26:59 PM