BISC 307L 2nd Edition Lecture 11 Current LectureTransmitters 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 sendsan 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 PSsubdivision, 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 arevarious 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. Forexample, 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 topostsynaptic 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 StructureIn the top picture, you can see a wholemuscle, where a single bundle of musclefibers called a fascicle has been furtherdissected out into fibers. The fiber is thecell - a multinucleated cell, arisen fromembryonic development by the fusion ofmany precursor cells, each contributingone nucleus.The bottom picture is of a short section ofmuscle fibers – they are composed ofbundles of myofibrils separated bymembranous structures. The bluemembrane surrounding the myofribril is the sarcoplasmic reticulum. The yellow T-tubules areinvaginations 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