Excitable Tissues د. طه صادق أحمد قسم علم وظائف الأعضاء كلية الطب جامعة الملك سعود الرياض 1

Q : What are the Excitable tissues ? They are nerve and muscle Q : Why are they called excitable ? Because they have large membrane potential (MP) and can produce measurable electrical responses when stimulated Which can be one of 2 types  ( 1) Local Response إستجابة محلية لا تنتقل لمسافة بعيدة Or (2) Action Potential نبضة كهربائية تنتقل بعيدا ) 2

__ _ _ _ - _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ __ _ _ _ _ __ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ __ _ _ _ ___ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ __ _ _ _ _ _ _ __ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ __ _ _ _ _ _ _ _ _ _ _ _ __ _ _ _ __ _ _ _ _ 0 Mv + + المسبار القياسي المسجّل ( النشط ) When both recording ( active) electrode ( active ) electrode and مرجعي reference electrode in ECF, potential= 0 mV مرجعي Nucleus Voltmeter

__ _ _ _ - _ _ _ _ _ _ _ _ _ _ _ _ _ _ __ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ __ _ _ _ _ _ _ _ _ _ _ _ _ __ _ _ _ ___ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ __ _ _ _ _ _ _ __ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ __ _ _ _ _ _ _ _ _ _ _ _ __ _ _ _ __ _ _ _ _ -90Mv + But when recording electrode enters the cell  an electrical potentials of = -70 to-90 mV there is recorded ( فولتاج أو بوتنشبال الخلية المرتاحة ) This is the Resting Membrane Potential (RMP). Nucleus

The Basis of the Resting Membrane Potential 5

Q: What are the types of membrane ionic channels ? (1) Leak ( Diffusion, Passive ) channels: are pores in the cell-membrane which are open all the time, therefore ions diffuse through them according to the ion Concentration Gradient. Because the concentration of sodium outside the cell is more than inside, the direction of the Na + chemical ( concentration ) gradient is inward  and, cosequently, sodium continuously diffuses through the Na + leak channels from outside ( the extracellular fluid, ECF) to inside the cell ( the intracellular fluid, ICF). On the other hand, because the concentration of K + is higher inside the cell than outsideF  the direction of the K + chemical ( concentration ) gradient is outward and, cosequently, K + continuously diffuses through the K + leak channels from inside to outside 6

Na and K Leak Channels

(B) Voltage-Gated channels : open when the cell- membrane is electrically activated Voltage-Gated Potassium Channel Voltage-Gated Sodium Channel

The cell-membrane is practically a semi-permeable membrane separating the ECF from the ICF. In the resting cell, Potassium leak channels are 50 times more leakier than sodium leak channels  therefore the RMP is closer to the Potassium Equilibrium Potential But in an active cell, during the AP, voltage-gated sodium channels open  the membrane becomes much more leakier to sodium than potassium.Therefore at the peak of AP we find the value of membrane potential closer to the Sodium Equilibrium Potential.. 9

و لكن : ما هو ال Equilibrium Potential of Na or K ? من أجل أن نفهم ذلك يجب أن نفهم فرضية نيرنست : Nernst Hypothesis 10

Nernst Hypothesis Nernst ( a Mathematician & Scientist ), hypothetically speaking, said that if : (1) the ECF and ICF contained ONLY one type of ion ( sodium or potassium ), & (2) the membrane is freely permeable ( 100% permeable ) to that ion Then he applied this hypothesis to sodium& to potassium, in turn  11

The Sodium Nernst ( Equilibrium ) Potential The cell-membrane is practically considered as a semi-permeable membrane separating the ECF from the ICF. Nernst made a hypothesis which was later verified mathematically as well as in the physics laboratory under artificial conditions. Nernst, hypothetically speaking, said that if we suppose that (1) the ECF and ICF contained ONLY sodium ion, (2) and that the cell-membrane was freely permeable to Na+ :  then Na+ will diffuse down its concentration gradient to the inside of the cell, carrying with it +ve charges, and progressively decreasing the negativity on the inner side of the membrane. As this goes on and on, and as the positive charges build inside, an opposing Electrical Potential begins to develop, tending to prevent the +ve Na+ from entering. This electrical potential will grow until it becomes strong enough to balance and counteract the concentration gradient which tends to push Na+ inside. When this electrical gradient ( force ), which tends to drive Na+ outside = the concentration gradient ( which tends to push Na+ in )  there will be no net Na+ movement across the membrane. The MP potential in that case is called Nernst Potential for Na+ ( or Na+ Equilibrium or Diffusion Potential ) = +61 mV. ( The charge always refers to the inside of the cell ). 12

The Potassium Nernst ( Equilibrium ) Potential (1) Similarly, if the ECF and ICF contained ONLY potassium ions  then K+ will diffuse down its concentration gradient ( via the K+ leak channels ) from inside the cell to outside, carrying with it +ve charges to the outside  thereby progressively increasing the negativity on the inner side of the membrane ( because we are losing +ve charges from inside ). At this goes on and on, and as negative charges build inside, an opposing electrical potential begins to develop, tending to prevent the exit of the +ve potassium ions 13

Q: What determines the value of the Equilibrium (Nernst) Potential of a given ion ( sodium or potassium ion ) ? A: It is the ratio of its concentration ( conc ) outside the cell divided by its concentration inside the cell. Q : How can we determine the value of Equilibrium Potentials of Sodium and Potassium ? Answer : by one of 2 ways A/ by calculation using Nernst Equation Which is  61 log conc in ECF / conc in ICF of that ion e.g., in case of potassium  And in case of sodium  B/ The other method for determining the Equilibrium Potential is by direct measurement in la boratory using electrodes 14

This electrical potential will grow until it becomes strong enough to balance and counteract the concentration gradient which tends to push K+ outsude. When this electrical gradient ( force ), which tends to keep K+ inside = the concentration gradient ( which tends to push K+ outside )  there will be no net K+ movement across the membrane. The MP potential in that case is called Nernst Potential for K+ ( or K+ Equilibrium Potential or Diffusion Potential ) = -94 mV. ( The charge always refers to the inside of the cell relative to the outside ) 15 The Potassium Nernst ( Equilibrium ) Potential (2)

Q: Why in the Resting Cell the value of the MP is closer to the Potassium equilibrium potential and in the active cell ( at the peak of the action potential ) it is closer to the Sodium equilibrium potential ? of the ion that has higher membrane permeability at that time. Therefore, in the resting cell, when the membrane permeability to K+ is more than its permeability to Na+  the value of the MP ( in that case of the resting cell we call it RMP ) = -70 to-90 mV ( which is closer to K+ equilibrium potential of – 94 mV ). By contrast, during the peak of AP, membrane permeability to Na becomes much more that that to K+, and the MP value = +35 mV, which is closer to the Na+ equilibrium potential of +61 mV ). 16

Origin of the RMP (1) Two questions should be asked : Q1: What are the 3 factors that make the inside of the cell negative ? Q2: and give the RMP the value of -70 to -90 mV ? Answer to both questions : the 3 factors are  (1) At rest, K+ leak channels are more effective than Na+ leak channels  more K+ diffuses to outside than Na+ to inside  i.e, the membrane is times more permeable to K+ than to Na+  more potassium lost than sodiumgained  net loss of +ve ions from inside the cell  more negative inside 17

( 2) Large intracellular anions ( proteins, sulphates & phosphates) have much higher concentration inside the cell than outside it (3) Active Transport : The sodium-potassium pump ( 3 Na+ pumped out in exchange for 2 K+ pumped in )  net loss of +ve charge from cell interior makes inner side of membrane negative 18

Thanks 19