2017-02-21_lecture 11 notes - Lecture 11 Autonomic Receptors(continued Introduction to Muscles Form and Function of Skeletal Muscles Brief review of

2017-02-21_lecture 11 notes - Lecture 11 Autonomic...

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Lecture 11: Autonomic Receptors (continued); Introduction to Muscles; Form and Function of Skeletal Muscles Brief review of neurotransmitter receptors (From lecture 10): As described previously, nicotinic cholinergic receptors are ionotropic (i.e., ligand-gated) ion channels that bind to acetylcholine. This receptor type is found on the dendrites and cell bodies of the postganglionic cells of the autonomic nervous system and the effector tissue (i.e., skeletal muscle) innervated by the somatic nervous system (although the nicotinic receptors between these two effector tissues differs). When acetylcholine binds to these receptors on a postsynaptic cell, the net effect is an excitatory postsynaptic potential. Acetylcholine will also bind to muscarinic cholinergic receptors on the effector tissues innervated by the postganglionic cells of the parasympathetic nervous system. Although there are several subtypes of muscarinic receptors, they are all metabotropic (I will discuss this in more detail later). The receptor is one of several types of G-protein-coupled receptors (GPCRs) that bind to extracellular acetylcholine. Lecture 11: GPCRs are integral proteins that are able to interact on the extracellular side with ligands such as acetylcholine, norepinephrine, and epinephrine, and on the intracellular side with G proteins. GPCRs are a broad family of receptors (i.e., approximately 800 in total!) that are targets for approximately 40% of pharmaceuticals target this broad class of receptor. G-proteins: their regulation and their nomenclature: G proteins, which are also known as guanine nucleotide-binding proteins, are critical regulators of intracellular signaling pathways. Their primary role is to serve as molecular switches by helping to stimulate the activity of different signaling pathways when one of a multitude of ligands bind to the extracellular domain of GPCRs. G-proteins consist of a trimeric complex of α, β, and γ subunits (known as Gα, Gβ, and Gγ, respect ively). We will describe how there are different isoforms of the alpha subunit, and these subunits differ in the signaling cascade they activate. G-proteins can exist in an inactive and in an active for, and this transition between these two states is mediated by the binding of an extracellular ligand to the GPCR. When no ligand is bound to a GPCR, the G protein will typically have guanosine diphosphate (GDP) (or when no guanine nucleotide is bound) to the alpha-subunit of the heterotrimeric G-protein complex. However, ligand binding to a GPCR receptor will cause the GDP molecule to dissociate from the G-protein and for guanosine triphosphate (GTP) is bound to the alpha subunit. GTP binding activates the G-protein complex. Upon activation of the G-protein, the G-protein dissociates from the GPCR, and the heterotrimeric subunits dissociate from one another. The G α subunit and the G ßγ subunits are now able to mediate many different cell-specific physiological process, including activating kinases and/or phosphatases, or opening or closing of ion channels. Shortly
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