BIOM 3090 Lecture Notes - Lecture 2: Nicotinic Acetylcholine Receptor, Signal Transduction, Skeletal Muscle
9 Jun 2018
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Major Receptor Families
Physiological receptors: signal transduction
- physiological receptors have 2 major functions
o ligand binding via ligand-binding domain
o message propagation via effector domain
- drugs modify cellular function after binding to receptor
o initiate, enhance, diminish, terminate (block)
- the receptor, its cellular target and any intermediary molecules are referred
to as the signal transduction pathway
o also called the receptor-effector coupling mechanism
Major types of drug receptors
- Transmembrane Ion channels
o Membrane lipid bilayers are largely impermeable (block passage of
fluid) to polar (charged) anions and cations
▪ Main ones are Na+, K+, Ca2+ and Cl-
o Ion channels have fundamental roles in neurotransmission (release of
neurotransmitter), cardiac conduction, muscle contraction, secretion
o Channels can be classified based on:
▪ Architecture (subunits)
▪ Ions conducted through the channel
▪ Mechanism of activation
• Ligand and voltage activated channels are major drug
targets
▪ Temo, ligand, voltage, stretch (mechanotransmission), storage
(of Ca2+)
o Ligand activated (gated) channels are diverse
▪ Major ligand gated channels found in the CNS
• Excitatory NTs (Ach and glutamate)
• Inhibitor NTs (glycine or GABA)
▪ Chemical gradient prefers Na+ movement inside cell
o The nicotinic acetylcholine receptor is a ligand gated channel
▪ Isoforms are found in the skeletal muscle and neurons
▪ Consists of 5 subunits (2-, , , ) in skeletal muscle
▪ In the closed state, the channel pore is occluded by bulky
amino acid side chains
▪ Full opening (activation) of the channel occurs with the
binding of 2 molecules of Ach to the subunits and a
conformational change → pore opening
▪ Na+ is the major electrolyte passes; K+ can also pass (but more
selective fir Na+)
o There are several types of voltage gated channels: Na+, K+, Ca2+ and
Cl1 → initiate AP in nerve and muscle cells
o Voltage activated Na+ channels initiate AP in nerve and muscle cells
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Document Summary
Physiological receptors have 2 major functions ligand binding via ligand-binding domain: message propagation via effector domain. Drugs modify cellular function after binding to receptor initiate, enhance, diminish, terminate (block) the receptor, its cellular target and any intermediary molecules are referred to as the signal transduction pathway: also called the receptor-effector coupling mechanism. Inhibitor nts (glycine or gaba: chemical gradient prefers na+ movement inside cell, the nicotinic acetylcholine receptor is a ligand gated channel. Isoforms are found in the skeletal muscle and neurons. Cl1 initiate ap in nerve and muscle cells: voltage activated na+ channels initiate ap in nerve and muscle cells, depolarize membrane from -70 mv (resting potential) up to. Islet beta-cell: k+ is normally leaking out of the channel when its open, when you close it the positive charge rises. Activates k+ channels (when you open a k_ channel you have hyperpolarization inhibits adenylyl cyclase.
