BISC 307L 2nd Edition Lecture 11 Current Lecture Transmitters and Receptors Traditional View The basic idea in anatomical pathways whether you are in the parasympathetic or sympathetic system follows the same basic plan a preganglionic neuron whose cell body is in the CNS sends an axon out to synapse onto a postganglionic neuron in the periphery which sends an axon to synapse onto a target cell These synapses between pre and postganglionic neurons are located in ganglia which can be separate discrete ganglia or ganglia that are scattered and embedded in the target tissue Shown above is the old inaccurate view of how the Autonomic Nervous System works In the PS subdivision the preganglion uses Ach Acetylcholine which binds to nAChRs nicotinic Ach receptors on the postsynaptic membrane This causes a permeability change so this ion gated receptor channel opens and allows Na and K through this generates a strong inward current and depolarizes the postganglionic neuron bringing it to threshold This mechanism results in a fast EPSP The PS postganglionic neuron releases Ach when excited but this Ach s target cells have muscarinic AChRs which are metabotropic not inotropic receptors So they initiate secondary messenger cascades and cause cellular response In the sympathetic system Ach is released and binds to nAChRs just like in the PS system but the postganglionic neuron has a different transmitter norepinephrine which binds to adrenergic receptors on target tissues of 2 basic types and several subtypes 2 alphas 3 betas Transmitters and Receptors Current View Evidence has been accumulating for this more current and accurate view Just like in the traditional view the first half of the process involving the preganglionic neuron is the same in both the sympathetic and parasympathetic subdivision ACh is the main neurotransmitter and there are nAChRs as well as mAChRs muscarinic in the postganglionic neuron this new idea is that you can have multiple receptors at the same site in the same membrane The mAChRs are metabotropic receptors and create a slowly developing EPSP or IPSP by modulating the K channel For example if it closes a previously opened K channel it would slowly cause depolarization EPSP Or if it were to open a K channel it would create a slowly developing IPSP Another new addition to this current view is that Ach is not the only neurotransmitter there are various peptides acting in the synapse that act as cotransmitters with Ach So in the PS subdivision the postganglionic neuron is excited and releases Ach which binds to mAChRs But many also release a peptide called VIP vasoactive intestinal peptide VIP binds to a VIP receptor and functions as a potent vasodilator It causes the relaxation of smooth muscle in blood vessels allowing blood pressure to inflate the vessel lowering vascular resistance and increasing blood flow The actions of these two transmitters ACh and VIP are synergistic For example in the salivary gland the PS nerves co release ACh and VIP ACh triggers salivary secretion while VIP triggers vasodilation in the blood vessels going to the secretory cells which causes more blood flow to help fluid movement out of the blood into the lumen of the salivary gland in order to get the secretions In the sympathetic division the principal neurotransmitter is norepi which binds to various adrenergic receptors But it has been discovered that some sympathetic nerves also release ACh which binds to nAChRs on target tissues An example would be sweat glands humans sweat when sympathetic nerves release Ach to sweat glands to cause sweating Many sympathetic postganglionic neurons can also co release peptides and ATP ATP can bind to postsynaptic ATP receptors on the target tissue or the ATP can get hydrolyzed all the way to adenosine which is also a transmitter and binds to purinergic receptors P1 P2 receptors Purinergic ATP and peptide effects are mostly metabotropic on the target tissue The effects however are complicated and different for different pathways The innervations of different organs are likewise complicated so it is important to know what type of innervation and postsynaptic receptor corresponds to which particular sympathetic effect a lot of illnesses are associated with malfunction in PS and S activity in certain glands Manipulating activity in these pathways by different antagonist receptor blockers is a fertile field for many pharmalogical interventions example Beta 1 receptors in the heart when they bind norepi would increase heart rate and is thusly a major regulator of heart rate And beta adrenergic blockers are used to control blood pressure routinely Skeletal Muscle Structure In the top picture you can see a whole muscle where a single bundle of muscle fibers called a fascicle has been further dissected out into fibers The fiber is the cell a multinucleated cell arisen from embryonic development by the fusion of many precursor cells each contributing one nucleus The bottom picture is of a short section of muscle fibers they are composed of bundles of myofibrils separated by membranous structures The blue membrane surrounding the myofribril is the sarcoplasmic reticulum The yellow T tubules are invaginations of the plasma membrane seen in the holes at the top of the structure So the lumen of the t tubule is continuous with the ECF In this picture we are zooming in on the myofibril and we can make out its molecular structure of thick filaments and thin filaments The thick filaments are bundles of myosin bottom left and the thin filaments is made up of actin subunits An actin subunit consists of a double helix of linear polymers bottom right two parallel strains twisted in a helix with different proteins like troponin and nebulin and titin that hold it together Tropomyosin and troponin play important regulatory roles as well Shown above is a single sarcomere the basic unit of a muscle You can see how from the Z disks thin filaments made of actin stick out and floating in the middle are the thick filaments made up of myosin There is interdigitation between the two of them The bottom half is to remind you that shortening of the muscle contraction is due to sliding of muscles over each other How do the filaments slide over each other And what controls this action The vertical purple things in top right which are the circular globular heads of myosin molecules They are reaching out to the thin filament across the space between the thick and thin When they bind to