1. Sodium Channels: The concentration of sodium ions outside the cell membrane is greater than that inside the cell. Therefore, there is a passive movement of sodium ions into the cell as the channels open. The sodium channels are voltage gated as they undergo conformational change in response to differences in potential across the membrane. The sodium channels have two types of gates that control the passage of sodium ions; the ‘H’ gate and the ‘M’ gate. At resting stage, the M gate is closed and the H gate is open. Upon stimulation by an action potential, the M gate opens and the channels become active, allowing sodium ions to travel into the cell. This opening of the channels is limited by time. After a fraction of a second, the H gates close spontaneously rendering the channels inactive. The sodium channels enter a refractory period during which they cannot be activated no matter how strong is the stimulus. At the same time, the M gate closes as well. As soon as the refractory period ends, the H channels open and the sodium channels are restored to their initial inactive state. The M gates remain closed till the arrival of the next action potential and the cycle is repeated.

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Different states of the fast sodium channels and relative conformational states of the H and M gates are summarized in the table below:




     Closed (Resting state)      Closed       Open
     Open (Active state)      Open       Open
     Inactivated      Open       Closed

2.Potassium Channels: Physiologically, the cells are loaded with potassium ions. The concentration of potassium ions is relatively greater inside the cell. As a result, they tend to move out of the cell from a region of higher concentration to a region of lower concentration until -94 mV is the potential difference across the membrane.


There are four types of potassium channels:

    • Potassium Leaky Channels: these are independent of any external factors and allow a constant leakage of potassium ions out of the cell.
    • Inward Rectifying Potassium Channels (IK1): These channels are voltage gated and they open or close in response to changes in membrane potential.
    • Inward Delayed Rectifying Potassium Channels: Also voltage gated.
    • Inward Rectifying Transient Potassium Channels: Open transiently for a very small amount of time.

3.Calcium Channels: The calcium ions tend to move inside the cell as they are present in greater amounts outside the cell. They are classified as fast and slow calcium channels.

4.Na/K ATPase: These are ATP dependent transmembrane proteins that actively pump sodium and potassium ions against their concentration gradient. 3 sodium ions are pumped out of the cell in exchange for 2 potassium ions into the cell. This creates a negative balance across the cell membrane which also corresponds to the negative RMP inside most cells.


  1. Rest State/Phase 4 of Action Potential: The Na/K ATPase works at the expense of energy to keep the resting membrane potential -90mV. Potassium leaky channels allow passive movement of potassium ions out of the cell in order to prevent excess negativity inside the cell and maintain the RMP.
  2. Rapid Depolarization/Phase 0 of Action Potential: Upon stimulation, the voltage dependent M gates of sodium channels open and rapidly allow sodium entry into the cells. An immediate spike in the positive direction is observed. The membrane potential rises from -90mV to +20mV. At this point, the H gates close and the sodium channels become refractory. The leaky potassium channels remain open.
  3. Transient Repolarization/Phase 1 of Action Potential: The inward rectifying transient potassium channels open. This happens for a very brief period of time during which potassium ions move out of the cell. A consequent drop in membrane potential is observed.
  4. Plateau/Phase 2 of Action Potential: The membrane potential remains constant during this part of the cycle as the resultant movement of ions in opposite directions balances the charge across the membrane. The calcium channels were triggered to open along with sodium ions at the start of the action potential. Due to their slow nature, the calcium channels take time to open. Opening of these channels and the movement of calcium ions inside the cell will oppose the negative charge produced by movement of potassium ions out of the cell. The movement of potassium ions is conducted by delayed rectifying potassium channels. Hence, the membrane potential is maintained at a constant value the entire time the calcium channels remain open.
  5. Repolarization/Phase 3 of Action Potential: At the end of Phase 2, the calcium channels start to close. The inward rectifying potassium channels open and along with the already open delayed rectifying potassium channels, they conduct potassium outflow. This would create a burst of positive charge leaving the cell. The membrane potential falls back to the RMP. The Na/K ATPase are reactivated to maintain RMP.


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