Adrenal MedullaTransmitters and Receptors (Traditional View)These synapses between the pre and post synaptic neurons are in the gangliaThis 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 APThe 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 adrenergicTransmitters and Receptors (Current view)More accurate viewAt 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 AcHIN parasympathetic postganglions, same as before except in addition to ACh released there is also VIP (vasoactive intestinal peptide) which is a vasodilatorVery 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 sweatingInappropriate activity in these pathways causes a lot of problemsBeta blockers are used to control blood pressure in this mechanismSkeletal MuscleSkeletal Muscle StructureFascicle and FiberT Tubules SR and Myofibril with z-diskStructure determines how it worksTop is a full muscle where a bundle of muscle fiber is the fascicle which is made up of fiberBelow is the fiber which is composed of myofibrils surrounded by sarcoplasmic reticulumSkeletal Muscle Structure 2Single myofibrilCell is striated (striped)Thick and thin filamentsThick = myosinThin= actin (helix with tropomyosin and troponin and nebulin)Skeletal Muscle Structure 3Shows a single sarcomere- from the Z disks thin filaments made of actin stick out and in the middle are thick filamentsThe bottom shows that force generation is due to sliding of the filaments over one anotherOval heads are the myosin heads and when they bind to the filament the are called cross bridgedcross Bridge CyclingEnzymatic and CYCLIC reaction. Remember what you know about proteins and enzymes and how they workThese 6 steps are arbitraryMyosin has two binding sites (for actin and ATP)Need to MG2+ ions alsoHow fast the cycle is determines howRate determining step is the ATP hydrolysis (ATPase activity determines how fast the muscle contracts)Step between 3 and 4 is the regulative step (depends on Ca2+)#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#2: Myosin head binds ATP lowering affinity of myosin head for actin so the head detaches (DETACHMENT). Myosin is an ATPase#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.#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#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 strongerNeuromuscular JunctionACh opens a non specific cation channelI(Na) + I(Ca) exceed I(K)Large EPSP (Endplate potential)Above is the muscle fiberWhite is the Schwann cell that covers itOn the right is the postsynaptic neuron and the muscle target tissue with Na+ channelsHighly effective reliable synapseLarge EPSP brings it to threshold generating a postsynaptic action potential taking down the fiberBISC 307L 1st Edition Lecture 10 Current Lecture- Adrenal Medullao- Transmitters and Receptors (Traditional View)o These synapses between the pre and post synaptic neurons are in the gangliao 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 inthe 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