Case Study: Some types of epilepsy are caused by a genetic mutation that produce
ID: 3516963 • Letter: C
Question
Case Study: Some types of epilepsy are caused by a genetic mutation that produces a voltage-gated sodium channel with a faster recovery from inactivation. You could probably tell me that this would increase the excitability or firing rate of the neuron and lead to seizure activity in the brain. However, we’ve created a sodium channel with a different mutation. It alters the voltage sensitivity of the sodium channel so that it only opens at more positive membrane potentials. Amazingly, it also leads to seizures, but we’re not sure how. Since you seem to have such a thorough grasp of neurophysiology, perhaps you will enlighten us.
a. If the threshold voltage of a neuronal cell membrane increases, how and why would the excitability of the neuron be affected?
Explanation / Answer
Voltage gated sodium channels acts as a gate for the diffusion of sodium cations across the plasmalemma. At resting potential, extracellular sodium concentration is ten times higher than the concentration inside a neuron, and the outer gate of the channel is closed. The closed position of the channel is termed its deactivated state. When the channel is subjected to a positive current, the charge induces conformational changes of the channel pore, opening the outer gate and activating the channel. As the gate opens, it provides a passage for an influx of sodium ions. This brief influx of positive charge flips the membrane polarity, and as the inner membrane passes the threshold level, the cell is depolarized and propagates an action potential. Within a fraction of millisecond, the inner gate closes to stop sodium from entering the neuron, the channel is inactivated. The channel's direct role in generating and propagating action potential across an entire neuron makes it a critical protein in maintaining functional neuronal electricity. Mutations in both of the sodium channel sub units, the pore forming alpha subunit and auxiliary beta subunit are linked to epilepsy.