Excitable Cells!

44b9d320267a3204e78af152243303c1?s=47 Kenrick Turner
November 12, 2017
51

Excitable Cells!

An overview of resting membrane potentials and action potentials.

44b9d320267a3204e78af152243303c1?s=128

Kenrick Turner

November 12, 2017
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Transcript

  1. Excitable cells!

  2. Topics • Ra$onale • Res$ng membrane poten$al • Ac$on poten$als

  3. Ra#onale Mul$cellular organisms need intercellular signalling Animals (cf. plants) need

    fast signalling Simple diffusion over long distances is slow
  4. Diffusion )me Diffusion is really slow over longer distances 1

    e.g. for K+ - 4 nm (cell membrane width) takes 4 nanoseconds - 1 cm takes 7 hours 1 is %me, is mean distance travelled, and is the diffusion coefficient of the substance
  5. Res$ng membrane poten$al The electrical poten.al difference across the membrane

    of a quiescent cell that is maintained when not conduc.ng impulses across it.
  6. Cell membrane Phospholipid bilayer Insulator with conduc0ng material on either

    side Res$ng poten$al -70 mV inside to out: 1. Selec've membrane permeability to ions due to channels • K+-selec've ion channels always open, so 100 x more permeable to K+ than Na+ 2. Different ionic concentra'ons on either side of membrane
  7. Establishing the RMP: the electrochemical gradient 1. K+-selec*ve ion channels

    • Passive diffusion of K+ down its concentra*on gradient (150mM -> 5mM) out of the cell 2. Na+/K+–ATPase • 3 Na+ out, 2 K+ in • Net movement of posi*ve charge out of the cell • Only directly contributes -4mV to the res*ng poten*al • However it establishes the chemical gradient of K+ and Na+ Na+ itself contributes li1le to the res3ng poten3al as the membrane is impermeable to it.
  8. Nernst equa+on Calculates the poten.al difference that an ion would

    produce over a permeable membrane 2 Simplifies at 18ºC for monovalent ions to: 2 is the equilibrium poten1al for a specific ion, the gas constant (8.314 J.K-1.mol-1), the temperature (K), Faraday's constant (96,500 C.mol-1), and the ionic valency (e.g. +1 for Na+)
  9. Ion Intracellular (mM) Extracellular (mM) Nernst poten5al (mV) K+ 150

    5 -90 Cl- 10 125 -70 Na+ 15 150 +60 As the membrane poten.al lies at –70mV, it's clear that another factor other than simple chemical gradient is involved in determining the poten.al difference – and that is the permeability of the membrane.
  10. Ac#on poten#als

  11. None
  12. Ac#on poten#als Rapid membrane depolarisa/on – a transient reversal of

    membrane polarity "All or none" response Generated by voltage–gated Na+ channels (blocked by tetrodotoxin ! and local anaesthe9cs) Threshold s*mulus: ~15 mV Dura%on: 2–3 ms
  13. Mechanism of ac-on poten-als 1. S$mulus depolarises membrane to theshold

    poten$al of –55 mV 2. Voltage–gated Na+ channels open 3. Na+ membrane permeability suddenly increases 4. This generates a larger poten$al difference than the s$mulus (–70 to +50 mV ≈ 120mV) 5. Voltage–gated Na+ channels rapidly inac$vate 6. Delayed ac$on voltage–gated K+ channels open 7. Membrane poten$al becomes nega$ve again as Na+ permeability falls and K+ permeability increases
  14. Features of ac,on poten,als Propoga'on is 2-stage: 1. Passive spread

    of depolarisa.on to the adjacent area of membrane via local currents 2. Regenera.on through the ac.on poten.al as the resultant poten.al difference is amplified back to full size Both posi%ve and nega%ve feedback loops are involved: • "All or none" effect is due to the posi3ve feedback loop between membrane depolarisa3on and Na+ permeability • Delayed ac3on voltage–gated K+ channels produce nega3ve feedback, returning membrane to its res3ng poten3al Only a small number of ions flow during channel opening – the change in membrane permeability is the most significant effect on poten;al difference, not the number of ions flowing
  15. Refractory period • Absolute refractory period: • Na+ channels are

    s8ll open and cell is completely inexcitable • Rela8ve refractory period: • 10–15 ms when a further ac8on poten8al can only be triggered by greater than normal s8muli
  16. Voltage–gated Na+ channel 4 domains of 6 α–helices Three states:

    1. Closed (res1ng) 2. Open (ac1on poten1al) 3. Inac1vated (refractory) Depolarisa*on causes charged S4 domain to move outwards, opening pore Opens for 0.7ms before inac2va2on Tetrodotoxin block the mouth from the outside LAs (ester & amide) block the channel a6er diffusing through the membrane
  17. Saltatory conduc-on Ac#ve conduc#on (ac#on poten#al) has a slower velocity

    of propoga#on than passive conduc#on due to the latency between threshold poten#al and full size depolarisa#on Cell membranes behave as capacitors as they are thin and hold charge well Myelin increases the resistance and reduces the capacitance of the membrane, so ac6on poten6als can only occur at nodes of Ranvier Between the nodes, local currents cause depolarisa3on of the next node (passive = faster) Myelin conserves energy due to the reduced ion flux requiring less energy to restore res5ng ionic concentra5ons
  18. Ventricular ac,on poten,al Longer in dura,on than in nerves (250ms

    vs 3ms) Dis$nct plateau phase of maintained depolarisa$on Lower res(ng membrane poten(al at –85 to –90 mV
  19. Ventricular ac,on poten,al • Phase 0: Rapid depolarisa-on by the

    fast from Na+ channels transiently opening • Phase 1: Par-al repolarisa-on – a rapid decrease in Na+ permeability • Phase 2: Plateau – slow Ca2+ channels open allowing inward flow of Ca2+, maintaining depolarisa-on and contrac-on • Phase 3: Repolarisa-on – Na+, K+, and Ca2+ permeabili-es return to normal • Phase 4: Res-ng – membrane poten-al governed mainly by potassium
  20. Sinoatrial node No res'ng state: intrinsic pacemaker poten'al generates autorhythmicity

    Maximum polarisa-on of –55 mV during diastole No Phase 1 or 2 as no plateau phase
  21. Sinoatrial node • Phase 4: Spontaneous diastolic depolarisa1on shi3s membrane

    to ac1on poten1al threshold by (slow influx of Ca2+) • Phase 0: Depolarisa1on by opening long-las1ng voltage- gated Ca2+ channels and inward movement of Ca2+ ( ). • No Na+ current involved at the SAN • Low peak depolarisa1on of 20mV • Phase 3: Repolarisa1on: • Reduc1on in depolarising currents ( & inac1vated at posi1ve poten1als) • Increase in repolarising currents ( ac1vated by posi1ve poten1als) causing late increase in K+ permeability (funny current) is a high background leak of Ca2+ through Na+ channels.
  22. Autonomic effects on SAN Parasympathe+cs increase K+ permeability in the

    SAN, hyperpolarising it and inhibi+ng spontaneous depolarisa+on. Sympathe)cs increase Ca2+ achieving the opposite effect.
  23. Thank you h"ps:/ /kenners.org/talks/excitable-cells

  24. None