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Essentials of Human Physiology for Pharmacy

Essentials of Human Physiology for Pharmacy

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20 <strong>Essentials</strong> <strong>of</strong> <strong>Human</strong> <strong>Physiology</strong> <strong>for</strong> <strong>Pharmacy</strong><strong>of</strong> the plasma membrane to potassium is high compared to that <strong>of</strong> sodium,the membrane potential approaches –90 mV.Next, consider a condition in which the membrane is permeable only tosodium. Because sodium is in a greater concentration outside the cell, the Na +ions initially diffuse into the cell down their concentration gradient. As a result,an excess <strong>of</strong> these positively charged ions accumulates in the ICF along theinternal surface <strong>of</strong> the plasma membrane; an excess <strong>of</strong> negative charges in the<strong>for</strong>m <strong>of</strong> the impermeable extracellular anion, chloride (Cl – ), remains outsidethe cell along the external surface <strong>of</strong> the plasma membrane. This inwardmovement <strong>of</strong> positive charges creates a positive membrane potential becausethe inside <strong>of</strong> the cell is now positive relative to the outside. However, as thepositively charged Na + ions continue to diffuse inward, once again an electricalgradient develops.The (+) charges that have accumulated in the ICF begin to repel anyadditional Na + ions and oppose the further movement <strong>of</strong> (+) charges inward.Instead, the positively charged Na + ions are now attracted to the negativelycharged Cl – ions remaining outside the cell. Eventually, the initial <strong>for</strong>cemoving Na + ions inward down their concentration gradient is exactly balancedby the subsequent <strong>for</strong>ce moving Na + ions outward down their electricalgradient, so there is no further net diffusion <strong>of</strong> sodium. The membranepotential at this point has reached the equilibrium potential <strong>for</strong> Na + (E Na+ ) andis equal to +60 mV. There<strong>for</strong>e, when the permeability <strong>of</strong> the plasma membraneto sodium is high compared to that <strong>of</strong> potassium, the membranepotential approaches +60 mV.At any given time, the membrane potential is closer to the equilibriumpotential <strong>of</strong> the more permeable ion. Under normal resting conditions, Na +ions and K + ions are permeable; however, potassium is significantly (50 to75 times) more permeable than sodium. There<strong>for</strong>e, a large number <strong>of</strong> K + ionsdiffuse outward and a very small number <strong>of</strong> Na + ions diffuse inward downtheir concentration gradients. As a result, the comparatively copious outwardmovement <strong>of</strong> K + ions exerts a powerful influence on the value <strong>of</strong> theresting membrane potential, driving it toward its equilibrium potential <strong>of</strong>–90 mV. However, the slight inward movement <strong>of</strong> Na + ions that would tendto drive the membrane potential toward its equilibrium potential <strong>of</strong> +60 mVrenders the membrane potential slightly less negative. The balance <strong>of</strong> thesetwo opposing effects results in a typical neuron resting membrane potential<strong>of</strong> –70 mV (see Figure 3.1).The Na + –K + pump also plays a vital role in this process. For each molecule<strong>of</strong> ATP expended, three Na + ions are pumped out <strong>of</strong> the cell into theECF and two K + ions are pumped into the cell into the ICF. The result is theunequal transport <strong>of</strong> positively charged ions across the membrane such thatthe outside <strong>of</strong> the cell becomes more positive compared to its inside; in otherwords, the inside <strong>of</strong> the cell is more negative compared to the outside.There<strong>for</strong>e, the activity <strong>of</strong> the pump makes a small direct contribution togeneration <strong>of</strong> the resting membrane potential.

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