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Lecture 2 and 3-AP

Lecture 2 and 3-AP - There are 2 major classes of ion...

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There are 2 major classes of ion channels in cell membranes A) Voltage-gated ion channels (VGC) require a change in membrane potential for the ion channel to open or close (RMP & AP) B) Ligand-gated ion channels (LGC) require a neurotransmitter (NT = ligand) to bind to a receptor (R) on the ion channel before the channel opens (EPP, EPSP’s & IPSP’s) + outside inside R NT (ligand)
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A family tree of voltage-gated channels Fig. 7-9 B&B
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Fig. 7-12a B&B The amino acids indicated by the solid circles are key determinants of the ion selectivity of the channel. Model of the voltage-dependent Na + channel protein. Intra-membrane cylinders 1-6 represent helices and there are 4 repeats (domains). pseudotetramer
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Fig. 7-12c BB K + channel tetramer
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Fig. 7-11c BB
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Fig. 7-11a BB
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Voltage Sensor and Pore Domain of K+ Channel Fig. 7-10 BB
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SUMMARY OF ION CHANNELS 1. Voltage-gated ion channels for Na + , K + , and Ca ++ are all part of one super- family. 2. Each ion channel consists of 4 subunits (or one pseudotetrameric subunit in the case of Na+ channel). Additional subunits (e.g. ) help provide selectivity, regulation, etc. 3. For a given ion, there are several types (isoforms) of each channel that are distributed differently among the cells of the body. 4. Each ion channel has a pore that is either open or closed depending on the position of subunits (gates). 5. Later on, we will discuss a number of drugs and poisons that block channels for specific ions and disrupt normal cellular function. 6. Whether a drug or poison blocks a channel depends on the isoform (subtype) of that channel. For example, tetrodotoxin blocks Na + channels in neurons and skeletal muscle cells but not in the heart.
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GENERATION OF ACTION POTENTIAL (AP)
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+ 0 - voltmeter mv [K + ] [K + ] + + + + + 70 + + + + + C E 3 Na+ 2 K+ ATP [Na+] [Na+] C E RMP = axon Electrical and concentration gradients for Na + and K + at rest (RMP)
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+ 0 - voltmeter mv [K + ] [K + ] + + + + + 70 + + + + + C E 3 Na+ 2 K+ ATP [Na+] [Na+] C E RMP = Steps required to initiate an AP 1. AP’s occur only in excitable cells such as neurons and muscle cells and require the membrane potential to reach or exceed the threshold of that cell membrane. 2. In response to stimulus, changes in membrane permeability (conductance) to Na + & K + via the opening and closing of specific voltage-gated channels generate AP. 3. At rest, the axon membrane is almost impermeable to Na + (closed Na + channels) and slightly permeable to K + (partially open K + channels). 4. Thus, the RMP of -70 mV is closer to the E K than E Na . axon
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+ 0 - voltmeter mv [K + ] [K + ] + + + + + 70 + + + + + C E 3 Na+ 2 K+ ATP [Na+] [Na+] C E RMP = A stimulus must be applied to an axon to generate an AP Depolarizing electrical stimulus 1. A depolarizing stimulus is applied to the membrane to produce a sub-threshold depolarization. axon Sub-threshold depolarization
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Time (msec) Memb. pot. (mv) 0 - 90 +100 + 65 E Na E K RMP - 70 Stimulus threshold Sub-threshold depolarization This stimulus produces a sub-threshold depolarization that is “CONDUCTED WITH DECREMENT”.
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