In: Biology
Hyperkalemic Periodic Paralysis (HPP) is a condition that produces periods of muscle weakness or paralysis. Despite its name (hyperkalemia means elevated K+), HPP is the result of a genetic mutation in voltage-gated sodium channels. Animals with HPP (horses get it, too) have a mutation in the gene that encodes the inactivation gate for voltage-gated Na+ channels.
a. For a normal action potential, please list the stages of the action potential, including the state of the gates AND the channel for BOTH the voltage-gated K+ AND Na+ channels. Use the following to guide your answers:
Stage of Action Potential | Inactivation Gate | Activation Gate | Channel |
b. The mutation in the voltage-gated Na+ channel allows the channel to recover from inactivation sooner than normal. You are working with cells expressing this mutation. What would happen to the ability of these neurons to generate action potentials? Would they generate more, fewer or the same number as a wild-type neuron? Explain, based on your understanding of voltage-gated channels that underlie the action potential, why this is the case.
a. - An action potential is generated when a stimulus changes the membrane potential to the values of threshold potential. The threshold potential is usually around -50 to -55 mV. It is important to know that the action potential behaves upon the all-or-none law. This means that any subthreshold stimulus will cause nothing, while threshold and suprathreshold stimuli produce a full response of the excitable cell.
Is an action potential different depending on whether it’s caused by threshold or suprathreshold potential? The answer is no. The length and amplitude of an action potential are always the same. However, increasing the stimulus strength causes an increase in the frequency of an action potential. An action potential propagates along the nerve fiber without decreasing or weakening of amplitude and length. In addition, after one action potential is generated, neurons become refractory to stimuli for a certain period of time in which they cannot generate another action potential.
Phases
An action potential has several phases; hypopolarization, depolarization, overshoot, repolarization and hyperpolarization.
Hypopolarization is the initial increase of the membrane potential to the value of the threshold potential. The threshold potential opens voltage-gated sodium channels and causes a large influx of sodium ions. This phase is called the depolarization. During depolarization, the inside of the cell becomes more and more electropositive, until the potential gets closer the electrochemical equilibrium for sodium of +61 mV. This phase of extreme positivity is the overshoot phase.
After the overshoot, the sodium permeability suddenly decreases due to the closing of its channels. The overshoot value of the cell potential opens voltage-gated potassium channels, which causes a large potassium efflux, decreasing the cell’s electropositivity. This phase is the repolarization phase, whose purpose is to restore the resting membrane potential. Repolarization always leads first to hyperpolarization, a state in which the membrane potential is more negative than the default membrane potential. But soon after that, the membrane establishes again the values of membrane potential.
Voltage-gated ion channels are a class of transmembrane proteins that form ion channels that are activated by changes in the electrical membrane potential near the channel. The membrane potential alters the conformation of the channel proteins, regulating their opening and closing. Cell membranes are generally impermeable to ions, thus they must diffuse through the membrane through transmembrane protein channels. They have a crucial role in excitable cells such as neuronal and muscle tissues, allowing a rapid and co-ordinated depolarization in response to triggering voltage change. Found along the axon and at the synapse, voltage-gated ion channels directionally propagate electrical signals. Voltage-gated ion-channels are usually ion-specific, and channels specific to sodium (Na+), potassium (K+), calcium (Ca2+), and chloride (Cl−) ions have been identified.[1] The opening and closing of the channels are triggered by changing ion concentration, and hence charge gradient, between the sides of the cell membrane.
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. The closing of the inactivation gate creates a refractory period within each individual Na+ channel. This refractory period eliminates the possibility of an action potential moving in the opposite direction back towards the soma. With its inactivation gate closed, the channel is said to be inactivated.
Voltage-activated K+ channels are integral membrane proteins containing a potassium-selective transmembrane pore gated by changes in the membrane potential. This activation gating (opening) occurs in milliseconds and involves a gate at the cytoplasmic side of the pore.
b - if the voltage gated sodium channels will inactivate sooner than normal then there will be less ability of neuron to generate action potential . Since channels are now closed the neuron will undergo into hyperpolarized state.