21:58 The inactivation gate actually closes shut by a voltage-independent mechanism. The mechanism is that the inactivation gate's ball domain is positively charged, while the core of the open ion channel is negatively charged (E and D residues stabilize the passage of cations). As soon as the channel opens, the core is exposed, causing the positive inactivation gate to bind the negatively charged ionophore core. The timing of this is orchestrated by the the length of the chain (of the ball-and-chain model), an intrinsically disordered domain that confers a negative change in entropy (and thus less favorable free energy change) upon folding. As chains folding is necessary for ball binding, the the longer the chain length, the lower the binding affinity, and thus the longer the latency period before the channel is inactivated. Appropriately, this is termed the "enrtopy clock." It is apt, because entropy is what points the arrow of time.
