Primary hyperkalemic periodic paralysis (HyperKPP) is an inherited disorder characterized by episodes of painful muscle contractions followed by periods of paralysis. Understanding the mechanisms behind the paralysis involves examining the effects of elevated extracellular potassium (K+) and the behavior of sodium channels in skeletal muscle cells.

Mechanism Behind Paralysis in Hyperkalemic Periodic Paralysis

• Elevation of extracellular K+ causes depolarization of skeletal muscle cells rather than hyperpolarization. This sustained depolarization leads to inactivation of voltage-gated sodium channels.

• Voltage-gated sodium channels become inactivated when the muscle membrane is depolarized, preventing further action potentials. This results in muscle fiber inexcitability and paralysis.

The mutations in HyperKPP affect the sodium channel SCN4A, impairing fast inactivation. This leads to persistent sodium influx, which depolarizes the muscle membrane continuously. In the presence of elevated K+ outside the cell, this membrane cannot repolarize effectively, causing a depolarization block that renders the muscle unable to contract.

Evaluating the Statements in the Question

• A. The elevation of extracellular K+ causes hyperpolarization of skeletal muscle cells: False. Elevated extracellular K+ causes depolarization, not hyperpolarization.

• B. The hyperpolarization of the muscle cell membrane inactivates sodium channels: False. Hyperpolarization generally removes inactivation; it is depolarization that causes inactivation.

• C. The elevation of extracellular K+ causes depolarization of skeletal muscle cells: True. This is the fundamental cause of membrane changes leading to paralysis.

• D. The sodium channels are voltage inactivated in depolarized state: True. Depolarization leads to voltage-dependent inactivation of sodium channels, stopping muscle excitability.

Correct Answer

The true statements are:

(4) C and D