Resting Membrane Potential (RMP)

What Is It?

• In large nerve fibers: -70 mV (Costanzo) to -90 mV (Guyton & Hall)
• The minus sign means the inside of the cell is negatively charged compared to the outside

"The resting membrane potential is the potential difference that exists across the membrane of excitable cells such as nerve and muscle in the period between action potentials."

• Costanzo Physiology, 7th Edition

Why Does It Exist? (The Ionic Basis)

Key ion concentrations at rest (Guyton & Hall):

• K+ is highly concentrated inside the cell (35x more inside than outside)
• Na+ is highly concentrated outside the cell (10x more outside than inside)
• At rest, the membrane is 100x more permeable to K+ than to Na+

Mechanism of Maintaining RMP - Step by Step (Simple Language)

Figure: Na+-K+ pump (left) and K+ leak channels (right) - Guyton & Hall

Step 1 - The Na+-K+ Pump Sets Up the Gradient

• Kicks 3 Na+ ions OUT of the cell
• Brings 2 K+ ions IN to the cell
• Net result: more positive charges leave than enter → inside becomes negative
• This creates a high K+ concentration inside and high Na+ concentration outside

Step 2 - K+ Leaks Out Through "Leak Channels"

Step 3 - An Electrical Force Pulls K+ Back In

• Chemical force pushing K+ out (concentration gradient)
• Electrical force pulling K+ back in (negative interior)

Step 4 - A Small Na+ Leak Shifts the Balance

Step 5 - The Na+-K+ Pump Adds a Final Touch

Figure 5.5 (Guyton & Hall): (A) K+ diffusion alone = -94 mV; (B) Adding Na+ leak = -86 mV; (C) Adding Na+-K+ pump = ~-90 mV

Summary Table

Two Roles of the Na+-K+ ATPase

1. Direct (electrogenic): Pumping 3 Na+ out vs. 2 K+ in directly makes the inside ~4 mV more negative
2. Indirect (most important): Maintains the K+ concentration gradient across the membrane, which drives the K+ diffusion potential that is the primary source of the RMP

"The Na+-K+ ATPase is necessary to create and maintain the K+ concentration gradient, which establishes the resting membrane potential."

• Costanzo Physiology, 7th Edition

Resting Membrane Potential - Super Simple Version

What Is It? (The Big Picture)

• Value: about -70 mV (the minus means inside is negative)

Why Is the Inside Negative?

You have a room (the cell). The room has a revolving door that only lets certain people out. Mostly, the K+ guys (potassium) can leave through the door. The Na+ guys (sodium) cannot easily enter.

1. There are lots of K+ inside the cell (140 units inside vs. only 4 outside)
2. K+ wants to escape - like people rushing out of a crowded room
3. K+ is positively charged, so when it leaves, the inside becomes more negative
4. Eventually, the inside gets so negative that it starts pulling K+ back in
5. The two forces (K+ wanting to leave vs. negative charge pulling it back) balance out
6. That balance point is the resting membrane potential

The Main Characters

How Is It Maintained? (The Na+-K+ Pump)

"Throw 3 Na+ OUT, let 2 K+ IN"

Why does this matter?

• 3 positive charges leave but only 2 positive charges enter
• So 1 extra positive charge is removed each cycle
• This keeps the inside slightly more negative
• It also keeps K+ stocked up inside and Na+ stocked up outside, ready for the next round of leaking

The Full Story in 4 Lines

1. The Na+-K+ pump packs K+ inside and Na+ outside
2. K+ leaks out through open channels (because there's so much of it inside)
3. This makes the inside negative
4. The pump keeps refilling K+ inside so the negativity is always maintained

A Simple Analogy

• The pump is someone constantly pouring water back in (K+)
• The leak channels are holes in the bucket letting water (K+) drip out
• The system never fully empties or overflows - it just stays at a steady level
• That steady level = the Resting Membrane Potential

Action Potential in Skeletal Muscle - Easy Language

Part 1 - The Nerve Fires the Muscle (Neuromuscular Junction)

Fig 5.6 - Guyton & Hall: The action potential waveform - notice the resting stage, sharp depolarization spike, overshoot, repolarization, and hyperpolarization.

Step-by-step at the neuromuscular junction:

1. Nerve impulse arrives at the nerve terminal (the motor end plate)
2. This opens voltage-gated Ca2+ channels in the nerve terminal
3. Ca2+ rushes in → causes acetylcholine (ACh) vesicles to fuse with the nerve membrane and dump ACh into the synaptic cleft (the tiny gap between nerve and muscle)
4. ACh binds to nicotinic receptors on the muscle membrane → opens ion channels
5. Na+ rushes in → muscle membrane depolarizes → this is the end-plate potential (EPP)
6. If EPP is big enough to cross threshold (~-55 mV), a muscle action potential fires
7. ACh is quickly destroyed by acetylcholinesterase so the signal doesn't last too long

Part 2 - The Action Potential in the Muscle Fiber Itself

Stage 1 - Resting (-80 to -90 mV)

Skeletal muscle RMP is about -80 to -90 mV - slightly more negative than neurons (-70 mV).

Stage 2 - Depolarization (the "upstroke")

• Stimulus pushes membrane to threshold (~-55 mV)
• Voltage-gated Na+ channels SNAP OPEN
• Na+ floods into the cell (Na+ is packed outside, positively charged)
• Inside goes from -80 mV → rushes past 0 mV → reaches +35 mV
• This is called the overshoot - the inside briefly becomes positive

Stage 3 - Repolarization (coming back down)

• Na+ channels automatically inactivate (they have a gate that snaps shut)
• Voltage-gated K+ channels NOW OPEN
• K+ rushes out of the cell (K+ is packed inside)
• Positive charges leave → inside becomes negative again
• Membrane returns toward -80 mV

Stage 4 - Hyperpolarization (brief undershoot)

• K+ channels stay open a tiny bit too long
• Too much K+ leaves → inside briefly goes more negative than resting (e.g., -90 mV)
• This is called hyperpolarization or the "undershoot"
• K+ channels then close → membrane returns to normal resting potential

Key numbers for Skeletal Muscle:

Part 3 - From Electrical Signal to Contraction (T-tubules & SR)

Fig 7.5 - Guyton & Hall: T-tubules dive deep into the fiber and sit right next to the sarcoplasmic reticulum's terminal cisternae.

How it works (Excitation-Contraction Coupling):

1. Action potential spreads along the sarcolemma (muscle surface membrane)
2. It dives deep inside via T-tubules (transverse tunnels that open to the outside and run through the whole fiber)
3. T-tubule has dihydropyridine (DHP) receptors that sense the voltage change
4. DHP receptors are physically linked to ryanodine receptors (RyR) on the sarcoplasmic reticulum (SR)
5. RyR channels open → Ca2+ is released from the SR in a flood
6. Ca2+ binds troponin → moves tropomyosin off actin → muscle contraction begins
7. After contraction, SERCA pump (Ca2+-ATPase) pumps Ca2+ back into the SR → muscle relaxes

The Whole Story in One Simple Chain:

Nerve impulse
      ↓
ACh released into synapse
      ↓
ACh binds nicotinic receptors on muscle
      ↓
Na+ enters → End-plate potential
      ↓
Threshold reached → Voltage-gated Na+ opens
      ↓
DEPOLARIZATION (inside goes positive)
      ↓
Na+ channels inactivate + K+ channels open
      ↓
REPOLARIZATION (inside goes negative again)
      ↓
K+ channels close → slight HYPERPOLARIZATION → back to rest
      ↓
Action potential travels along sarcolemma + into T-tubules
      ↓
DHP receptor → Ryanodine receptor → Ca2+ floods out of SR
      ↓
Ca2+ + Troponin → MUSCLE CONTRACTS
      ↓
SERCA pump removes Ca2+ → MUSCLE RELAXES