1

Membrane Potentials (Polarity)

• Information found in 2 places: – Chapter 3 - pp. 79 - 81– Chapter 9 - pp. 286-289

6/22/12MDufilho

MDufilho

Generation of a Resting Membrane Potential

• Resting membrane potential (RMP)– Produced by separation of oppositely charged

particles (voltage) across membrane in all cells

• Cells described as polarized

– Voltage (electrical potential energy) only at membrane

• Ranges from –50 to –100 mV in different cells– "–" indicates inside negative relative to outside

6/22/12 2

3

Membrane Potentials - Introduction

What you must know 1. Locations of ECF vs. ICF

2. Normal distribution of Na+, K+, Cl-, Ca++ and proteins between ECF vs. ICF

3. Cell membranes are much more permeable to K+ than Na+

4. Composition of ECF is different from that of ICF, but both are electrically neutral and isotonic

6/22/12MDufilho

MDufilho

Figure 3.15 The key role of K+ in generating the resting membrane potential.

1 K+ diffuse down their steepconcentration gradient (out of the cell)via leakage channels. Loss of K+

results in a negative charge on theinner plasma membrane face.

2 K+ also move into the cellbecause they are attracted to thenegative charge established on theinner plasma membrane face.

3 A negative membrane potential(–90 mV) is established when themovement of K+ out of the cell equalsK+ movement into the cell. At thispoint, the concentration gradientpromoting K+ exit exactly opposes theelectrical gradient for K+ entry.

Extracellular fluid

Potassiumleakagechannels

Protein anion (unable tofollow K+ through themembrane)Cytoplasm

++

+ + + ++ +

––

–––––

–

Slide 1

6/22/12 4

Normal Distribution of Electrolytes

Ions ICF (mM/Liter) ECF (mM/Liter) mV

• Na+ 15 150 - 70

• K+ 150 5 - 90

• Cl- 10 125

• Ca++ 0.1 cytosol Higher in SR -1000

6/22/125MDufilho

MDufilho

Selective Diffusion Establishes RMP

• In many cells Na+ affects RMP– Attracted into cell due to negative charge

RMP to –70 mV – Membrane more permeable to K+ than Na+, so

K+ primary influence on RMP

• Cl– does not influence RMP—concentration and electrical gradients exactly balanced

6/22/12 6

Figure 11.8

Finally, let’s add a pump to compensate for leaking ions.Na+-K+ ATPases (pumps) maintain the concentration gradients, resulting in the resting membrane potential.

Suppose a cell has only K+ channels...K+ loss through abundant leakagechannels establishes a negativemembrane potential.

Now, let’s add some Na+ channels to our cell...Na+ entry through leakage channels reducesthe negative membrane potential slightly.

The permeabilities of Na+ and K+ across the membrane are different.

The concentrations of Na+ and K+ on each side of the membrane are different.

Na+

(140 mM )K+

(5 mM )

K+ leakage channels

Cell interior–90 mV

Cell interior–70 mV

Cell interior–70 mV

K+

Na+

Na+-K+ pump

K+

K+K+

K+

Na+

K+

K+K

Na+

K+K+ Na+

K+K+

Outside cell

Inside cellNa+-K+ ATPases (pumps) maintain the concentration gradients of Na+ and K+

across the membrane.

The Na+ concentration is higher outside the cell.

The K+ concentration is higher inside the cell.

K+

(140 mM )Na+

(15 mM )

6/22/127MDufilho

8

What happens to establish resting membrane potential

• K+ diffuses out of cell – Why?

• Protein anions do not diffuse – Why?

• Therefore membrane interior becomes more negative

• Negativity becomes great enough to attract K+ back into the cell

• When K+ concentration gradient is balanced by membrane potential (-70mV) one K+ enters cell as one leaves

• The tendency for K+ to diffuse out of the cell is the most significant factor in establishing RMP

6/22/12MDufilho

9

How to Alter Resting Membrane Potential

• Alter the permeability to one or more ions

• This typically happens at a chemical synapse

6/22/12MDufilho

MDufilho

Figure 9.8 When a nerve impulse reaches a neuromuscular junction, acetylcholine (ACh) is released. Slide 1

Actionpotential (AP)

Myelinated axonof motor neuron

Axon terminal of neuromuscular junction

Sarcolemma ofthe muscle fiber

Synaptic vesiclecontaining ACh

Synaptic cleft

Junctionalfolds of sarcolemma

Sarcoplasm ofmuscle fiber

Postsynaptic membraneion channel opens;ions pass.

Ion channel closes;ions cannot pass.

Action potential arrives at axon terminal of motor neuron.

Voltage-gated Ca2+ channels open. Ca2+ enters the axon terminal moving down its electochemical gradient.

Ca2+ entry causes ACh (aneurotransmitter) to be releasedby exocytosis.

ACh diffuses across the synaptic cleft and binds to its receptors on the sarcolemma.

ACh binding opens ionchannels in the receptors thatallow simultaneous passage ofNa+ into the muscle fiber and K+

out of the muscle fiber. More Na+

ions enter than K+ ions exit,which produces a local changein the membrane potential calledthe end plate potential.

ACh effects are terminated byits breakdown in the synapticcleft by acetylcholinesterase anddiffusion away from the junction.

Axon terminalof motor neuron

Fusing synaptic vesicles

Degraded AChACh

Acetylcho-linesterase

ACh

4

3

2

1

5

6

6/22/12 10

11

Action Potential

• A transient depolarization event that includes polarity reversal of a membrane and the propagation of an action potential along the membrane

6/22/12MDufilho

MDufilho

Figure 9.9 Summary of events in the generation and propagation of an action potential in a skeletalmuscle fiber.

Slide 1Open Na+

channel

Na+

Closed K+

channel

K+

Action potential

Axon terminal ofneuromuscularjunction

ACh-containingsynaptic vesicle

Ca2+

Ca2+

Synapticcleft

Wave ofdepolarization

An end plate potential is generated at theneuromuscular junction (see Figure 9.8).

Depolarization: Generating and propagating an actionpotential (AP). The local depolarization current spreads to adjacentareas of the sarcolemma. This opens voltage-gated sodium channelsthere, so Na+ enters following its electrochemical gradient and initiatesthe AP. The AP is propagated as its local depolarization wave spreads toadjacent areas of the sarcolemma, opening voltage-gated channels there.Again Na+ diffuses into the cell following its electrochemical gradient.

Repolarization: Restoring the sarcolemma to its initialpolarized state (negative inside, positive outside). Repolarizationoccurs as Na+ channels close (inactivate) and voltage-gated K+ channelsopen. Because K+ concentration is substantially higher inside the cellthan in the extracellular fluid, K+ diffuses rapidly out of the muscle fiber.

1

2

3

Closed Na+

channelOpen K+

channel

Na+

K+

−−−−−−−−−−−−−−−−−−−

−−−−

−−−−−−−− −−−−−−−−−−−−

6/22/12 12

13

• Time from the opening of the Na+ activation gates until the closing of inactivation gates

• The absolute refractory period:– Prevents the neuron from generating an

action potential– Ensures that each action potential is separate– Enforces one-way transmission of nerve

impulses

Absolute Refractory Period

6/22/12MDufilho

14

• The interval following the absolute refractory period when:– Sodium gates are closed– Potassium gates are open– Repolarization is occurring

• The threshold level is elevated, allowing strong stimuli to increase the frequency of action potential events

Relative Refractory Period

6/22/12MDufilho

MDufilho

Figure 9.10 Action potential tracing indicates changes in Na+ and K+ ion channels.

Mem

bra

ne p

ote

nti

al (m

V) +30

0

–95

0 5 10 15 20

Depolarizationdue to Na+ entry

Na+ channelsclose, K+ channelsopen

Repolarizationdue to K+ exit

K+ channelsclosed

Na+

channelsopen

Time (ms)6/22/12 15

16

What if ……..?

1. The amount of extracellular K+ were below normal?

2. The release of the NT from the synaptic knob were prevented?

3. Receptor sites for the NT were blocked?

4. The amount of EC Ca++ were below normal

5. The number of NT receptor sites were reduced?

6. Opening of the voltage-gated sodium channels were prevented?

7. You grab a live 120V electric wire?

6/22/12MDufilho