BISC 307L 1st Edition Lecture 10 Current Lecture Adrenal Medulla o Transmitters and Receptors Traditional View o These synapses between the pre and post synaptic neurons are in the ganglia o This is the old and accurate view on how the autonomic nervous system works In the parasympathetic division the preganglion uses ACh and binds to nicotinic receptors on the postganglion When ACh binds to receptor there is a permeability change and a channel opens that is permanently open to K and Na ions and causes a fast EPSP which will generate an AP The postganglionic neuron when excited also releases ACh but this ACh now binds to muscarinic receptors which are metabotropic receptors In the sympathetic system it is the same as the parasympathetic in the preganglion but in the postganglion the neurotransmitter is Norepinephrine which binds to alpha1 2 beta 1 2 and ARs which are adrenergic Transmitters and Receptors Current view o More accurate view At ganglion in both parasympathetic and sympathetic ACh is released to bind to nicotinic receptors AND muscarinic receptors on the postganglion These muscarinic receptors generate a slowly developing EPSP which is done by modulation of K channels closes previously open K channels depolarizing the channel OR closes K channels causing slow IPSP Also ACh is not the only transmitter at the synapse but also various peptides that are co transmitters with AcH IN parasympathetic postganglions same as before except in addition to ACh released there is also VIP vasoactive intestinal peptide which is a vasodilator Very active in salivary gland parasympathetic In Sympathetic postganglion side the principle neurotransmitter is norepinephrine as before but also now know ACh is involved They also co release ATP which can bind to ATP receptors or is actively hydrolyzed to adenosine which is also a neurotransmitter and binds to purinergic receptors Stimulates sweating Inappropriate activity in these pathways causes a lot of problems Beta blockers are used to control blood pressure in this mechanism Skeletal Muscle Skeletal Muscle Structure o Fascicle and Fiber o T Tubules SR and Myofibril with z disk o Structure determines how it works o Top is a full muscle where a bundle of muscle fiber is the fascicle which is made up of fiber o Below is the fiber which is composed of myofibrils surrounded by sarcoplasmic reticulum Skeletal Muscle Structure 2 o o Single myofibril o Cell is striated striped o Thick and thin filaments Thick myosin Thin actin helix with tropomyosin and troponin and nebulin Skeletal Muscle Structure 3 o o o Shows a single sarcomere from the Z disks thin filaments made of actin stick out and in the middle are thick filaments o The bottom shows that force generation is due to sliding of the filaments over one another o Oval heads are the myosin heads and when they bind to the filament the are called cross bridged cross Bridge Cycling o Enzymatic and CYCLIC reaction Remember what you know about proteins and enzymes and how they work o These 6 steps are arbitrary o Myosin has two binding sites for actin and ATP o Need to MG2 ions also o How fast the cycle is determines how o Rate determining step is the ATP hydrolysis ATPase activity determines how fast the muscle contracts o Step between 3 and 4 is the regulative step depends on Ca2 o 1 Myosin head has nothing bound to it except actin No nucleotide ATP or ADP bound Without ATP bound it has a high affinity for binding actin this is called the RIGOR state Doesn t stay in it very long o 2 Myosin head binds ATP lowering affinity of myosin head for actin so the head detaches DETACHMENT Myosin is an ATPase o 3 ATPase activity of myosin head hydrolyzes ATP to ADP which releases energy That energy 10 is transferred to the myosin molecule resulting in a change in conformation of myosin The angle of the head changes from 45 degrees to about 90 degrees ADP and phosphate are still attached o 4 ADP inhibits binding of myosin to actin but much less so so the head can attach again in a much weaker attachment Now since the head is at 90 degrees it is attached to the second molecule REATTACHMENT Causes myosin to lose affinity for phosphate and the phosphate comes off o o o 5 When phosphate comes off this changes the conformation of myosin head again and changes to 45 degree angle but since head is attached this causes it to pull the thin filament along 6 IN this configuration the myosin has a low affinity for ADP so the ADP comes off and now were back to number one and the binding to actin becomes stronger Neuromuscular Junction o ACh opens a non specific cation channel I Na I Ca exceed I K Large EPSP Endplate potential o o Above is the muscle fiber o White is the Schwann cell that covers it o On the right is the postsynaptic neuron and the muscle target tissue with Na channels o Highly effective reliable synapse o Large EPSP brings it to threshold generating a postsynaptic action potential taking down the fiber
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