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Unformatted text preview: BMEN E4001x: Quantitative Physiology I / Molecular and Cellular Systems Notes 10 - Excitable membranes B&B Chapter 7 Consider two manipulations: hyperpolarization : current is pulled (holes are pulled, electrons are injected) to make the potential more negative than resting. The result is typically a graded response , in which the membrane adjusts to accommodate the new electrical state. Higher injection rate, higher deviation from the non-current resting potential. depolarization : current is pushed (holes injected, electrons pulled) to raise the intracellular voltage. In some cells, this is met with a graded response. In electrically excitable cells, this is met with a stereotypical excursion, the action potential There are many, many, many manipulations that can happen using the patch clamp technique, but we’ll first consider the case in which a current is injected to initiate the action potential, then voltage is watched to follow the cell membrane behavior. The stereotypic voltage, read at a single position of the membrane, is shown below: It consists of multiple phases, including: Depolarization and Threshold: when the membrane voltage crosses this level, the voltage now takes off precipitously towards higher voltages. Peak: at some point, the voltage peaks, then begins to become more negative. The peak voltage is often greater than zero. Repolarization: Voltage drives back towards resting, with several subphases. The final potential is often lower than the initial resting potential; this is called hyperpolarization. The duration of this entire sequence can range from a few milliseconds to something on the order of a second, depending on the specific cell type, species, pathology. The specific levels that these voltages correspond to can also vary with any of a huge range of variables. This feature travels at 5-25 m/s. At any given point, an AP in squid axon is only a few milliseconds. Thus, the entire feature has an extent on the order of millimeters to centimeters. In the absolute refractory period, another action potential simply cannot be initiated. In the relative refractory period, it is possible to initiate a new action potential, but requires more current/duration. Our goal here is to explore some of the molecular aspects of this relative to our discussion on membranes, specific implementations in specific physiological systems, including the propagating nature of this in neurons, is the domain of QPII. Much of the pioneering work was done in the giant squid axon, due to it’s size and accessibility. The ion composition in this system is a bit different than the mammalian cell, but Nernst potentials are quite close: Ion concentration (mM) interstitial space cell (“typical”) V nernst (mV) Na + , mammalian cell 145 15 +59 (37C) K + , mammalian cell 4.5 120-71 (37C) Na + , squid giant axon 440 50 +54 (15C) K + , squid giant axon 20 400-75 (15C) • As we have been discussing, the resting potential suggests that the cell is not at...
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- Fall '10
- squid axon, QPII