<P> Voltage - gated Na channels have three main conformational states: closed, open and inactivated . Forward / back transitions between these states are correspondingly referred to as activation / deactivation (between open and closed, respectively), inactivation / reactivation (between inactivated and open, respectively), and recovery from inactivation / closed - state inactivation (between inactivated and closed, respectively). Closed and inactivated states are ion impermeable . </P> <P> Before an action potential occurs, the axonal membrane is at its normal resting potential, and Na channels are in their deactivated state, blocked on the extracellular side by their activation gates . In response to an electric current (in this case, an action potential), the activation gates open, allowing positively charged Na ions to flow into the neuron through the channels, and causing the voltage across the neuronal membrane to increase . Because the voltage across the membrane is initially negative, as its voltage increases to and past zero, it is said to depolarize . This increase in voltage constitutes the rising phase of an action potential . </P> <P> At the peak of the action potential, when enough Na has entered the neuron and the membrane's potential has become high enough, the Na channels inactivate themselves by closing their inactivation gates . The inactivation gate can be thought of as a "plug" tethered to domains III and IV of the channel's intracellular alpha subunit . Closure of the inactivation gate causes Na flow through the channel to stop, which in turn causes the membrane potential to stop rising . With its inactivation gate closed, the channel is said to be inactivated . With the Na channel no longer contributing to the membrane potential, the potential decreases back to its resting potential as the neuron repolarizes and subsequently hyperpolarizes itself . This decrease in voltage constitutes the falling phase of the action potential . </P> <P> When the membrane's voltage becomes low enough, the inactivation gate reopens and the activation gate closes in a process called deinactivation . With the activation gate closed and the inactivation gate open, the Na channel is once again in its deactivated state, and is ready to participate in another action potential . </P>

When do the sodium voltage gated channels first become inactivated
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