Overview
This lecture explains the activation cycle of voltage-gated sodium channels, describing their structural features and the sequence of functional states during neuronal signaling.
Structural Features of Voltage-Gated Sodium Channels
- Voltage-gated sodium channels have four voltage sensor domains containing positively charged amino acids sensitive to membrane potential.
- The core of the channel contains pore-forming domains that host the selectivity filter, which makes the channel selective for sodium ions.
- The voltage gate is also located in the pore-forming domain and regulates channel opening and closing.
- An inactivation gate acts as a hinged lid that can block the channel pore and stop ion flow.
Functional States of Sodium Channels
- Sodium channels exist in three states: closed, open, and inactivated.
- In the closed state, the membrane potential is negative, voltage sensors are pulled inward, and the voltage gate is shut, blocking sodium flow.
- Depolarization (less negative membrane potential) causes voltage sensors to move outward, opening the voltage gate and allowing sodium to enter the cell.
- Briefly after opening, the inactivation gate swings shut, blocking the channel despite the voltage gate being open; this is the inactivated state.
- Repolarization (return to a negative potential) moves voltage sensors inward, closes the voltage gate, and resets the inactivation gate to reopen the channel.
Activation Cycle Sequence
- The channel transitions unidirectionally: closed → open → inactivated → closed.
- Opening allows sodium influx during action potentials, followed by rapid inactivation to prevent prolonged depolarization.
- Channels are ready for reactivation only after returning to the closed state via repolarization.
Key Terms & Definitions
- Voltage Sensor — Channel region sensitive to electrical membrane potential, containing positively charged amino acids.
- Pore-Forming Domain — Channel region forming the pathway for ion flow and containing the selectivity filter and voltage gate.
- Selectivity Filter — Structure in the pore-forming domain that makes the channel specific to sodium ions.
- Voltage Gate — Part of the channel that opens or closes in response to voltage sensor movement.
- Inactivation Gate — Hinged structure that quickly blocks the channel after opening.
- Depolarization — Decrease in membrane negativity, triggers channel opening.
- Repolarization — Restoration of negative membrane potential, resets channel to closed state.
Action Items / Next Steps
- Review the sequence of channel state transitions: closed, open, inactivated, and back to closed.
- Study the role of sodium channels in the action potential for upcoming classes.