SECTION I CELLULAR PHYSIOLOGY Primary Hyperkalemie Periodic Paralysis A 10-year-old hoy has sporadic attacks of muscle paralysis.The patient has four brothers,all of whom have suffered sinilar symptons.The onset of these attacks is characterized by pain associated with contractures of the affected museles.Later in the attack those muscles may become paralyzed and nore flaccid.Episodes of pain and contracture freqmently occur without subsequent paralysis.Analysis of blood samples taken during an attack indicates that the patient is hyperkalemic.Plasma K+levels are normal when the patient is not having an attack.Biopsies of the patient's mascle show a significantly diminished level of intracellular K+(83 mol/kg wet tissue)compared vith control muscle (95 mmol/kg wet tissue).Basal tissue activity of Nat.K+-ATPase is normal.Paralytic attacks are accompanied by diuresis with increased K+excretion.Electrophysiologic studies of the patient show that during an attack the exeitability and conduction times of motor neurons are normal,as is the function of the neuromuscular junction.Microelectrode studies show that during an attack the magmitude of the resting merbrane potential of skeletal muscle cells is diminished compared with control muscle fibers. Electromyography shows that early in an attack the muascle coetractures are associated with spontameous action potentials in the affected muscle fibers.Later, during the paralytic phase of an attack.muscle cells becone electrically inexcitable-the muscle cells do not respond electrically to stimulation of the motor axons that innervate them.A paralytic attack can be relieved by treating the patient with an insulin injection.Long-term adinistration of the B2-agonist salbutanol dramatically diminishes the occurrence of episodes of both contractures and subsequent paralytie attacks
SECTION I CELLULAR PHYSIOLOGY Primary Hyperkalemic Periodic Paralysis A 10-year-old boy has sporadic attacks of muscle paralysis. The patient has four brothers, all of whom have suffered similar symptoms. The onset of these attacks is characterized by pain associated with contractures of the affected muscles. Later in the attack those muscles may become paralyzed and more flaccid. Episodes of pain and contracture frequently occur without subsequent paralysis. Analysis of blood samples taken during an attack indicates that the patient is hyperkalemic. Plasma K+ levels are normal when the patient is not having an attack. Biopsies of the patient's muscle show a significantly diminished level of intracellular K+ (83 mmol/kg wet tissue) compared with control muscle (95 mmol/kg wet tissue). Basal tissue activity of Na+, K+-ATPase is normal. Paralytic attacks are accompanied by diuresis with increased K+ excretion. Electrophysiologic studies of the patient show that during an attack the excitability and conduction times of motor neurons are normal, as is the function of the neuromuscular junction. Microelectrode studies show that during an attack the magnitude of the resting membrane potential of skeletal muscle cells is diminished compared with control muscle fibers. Electromyography shows that early in an attack the muscle contractures are associated with spontaneous action potentials in the affected muscle fibers. Later, during the paralytic phase of an attack, muscle cells become electrically inexcitable─the muscle cells do not respond electrically to stimulation of the motor axons that innervate them. A paralytic attack can be relieved by treating the patient with an insulin injection. Long-term administration of the β2-agonist salbutamol dramatically diminishes the occurrence of episodes of both contractures and subsequent paralytic attacks
1.What might account for the patient being hyperkalemic during an attack,while the potassium concentration in his skeletal muscle cells is diminished?What types of alterations of basic cellular processes might underlie this situatioe? 2.What explains the observation that the magnitude of the resting merbrane potentials of the patient's skeletal muscle fibers is diminished during am attack? 3.Does the dininished resting merbrane potential have anything to do with the spontaneous action potentials and contractures that occur early in an attack,before paralysis sets in? 4.How might the diminished resting nembrane potential contribute to the paralytic phase of an attack,in which muscle cells are electrically inexcitable? 5.How might insulin terninate a paralytic attack? 6.How might long-term adninistration of salbutanol diminish the occurrence of attacks of contractures and paralysis? ANSVER 1.The hyperkalemia with a conconitant decrease in the anount of K+in muscle cells suggests that the hyperkalemia is caused by K+efflux froa the cells,but the cause of Kt efflux is not known.Net Kt efflux fron muscle cells night occur because of diminished rate of K+accumulation by the Na+.K+-ATPase,or an increased rate of K+efflux fron the cell,or a combination of both factors.The observation that Na+,K+-ATPase is normal does not completely rule out a malfunetion of this protein during an attack. 2.Elevating extracellular K+and decreasing the intracellular level of K+would decrease the potassfum equilibrium potential and thus decrease the magnitude of the resting menbrane potential. 3.The decreased mgnitude of the resting menbrane potential initially brings the muscle cells closer to threshold for firing an action potential.For this reason, spontaneous.small fluctuations in the resting membrane potential may reach threshold.This results in spontaneous action potentials and contractions of
1. What might account for the patient being hyperkalemic during an attack, while the potassium concentration in his skeletal muscle cells is diminished? What types of alterations of basic cellular processes might underlie this situation? 2. What explains the observation that the magnitude of the resting membrane potentials of the patient's skeletal muscle fibers is diminished during an attack? 3. Does the diminished resting membrane potential have anything to do with the spontaneous action potentials and contractures that occur early in an attack, before paralysis sets in? 4. How might the diminished resting membrane potential contribute to the paralytic phase of an attack, in which muscle cells are electrically inexcitable? 5. How might insulin terminate a paralytic attack? 6. How might long-term administration of salbutamol diminish the occurrence of attacks of contractures and paralysis? ANSWER 1. The hyperkalemia with a concomitant decrease in the amount of K+ in muscle cells suggests that the hyperkalemia is caused by K+ efflux from the cells, but the cause of K+ efflux is not known. Net K+ efflux from muscle cells might occur because of diminished rate of K+ accumulation by the Na+, K+-ATPase, or an increased rate of K+ efflux from the cell, or a combination of both factors. The observation that Na+, K+-ATPase is normal does not completely rule out a malfunction of this protein during an attack. 2. Elevating extracellular K+ and decreasing the intracellular level of K+ would decrease the potassium equilibrium potential and thus decrease the magnitude of the resting membrane potential. 3. The decreased magnitude of the resting membrane potential initially brings the muscle cells closer to threshold for firing an action potential. For this reason, spontaneous, small fluctuations in the resting membrane potential may reach threshold. This results in spontaneous action potentials and contractions of
skeletal muscle cells and leads to the contractures experfenced by the patiemt early in an attack. 4.Prolonged depolarization of the muscle cell plasma merbrane will lead to voltage inactivation of Na+chanmels in the menbrane,which will result in the muscle cell's being unable to fire an action potential.This is believed to be the cause of the paralytic phase of an attack and is supported by the observation that during the paralytic phase,the patient's skeletal muscle cells nay be electrically inexcitable. 5.Insulin immediately and powerfully promotes the uptake of K+by cells and the extrusion of Nat from cells.Administration of insulin thus corrects the hyperkalenia,restores cellular K+levels toward normal,and causes the resting membrane potential for the affected skeletal muscle cells to becoee closer to the normal resting value.In this way insulin is believed to terminate an attack of contractures or paralysis in these patients. 6.Long-term adninistration of salbutanol.a B 2-agonist,increases the activity of the Nat,K+-ATPase in skeletal muscle cells.In this way,salbutanol administration leads to increased sequestration of K+in muscle cells.Apparemtly this helps to prevent the K+efflux that underlies episodes of hyperkalenia with resultant comtractures that may be fol lowed by periods of paralysis
skeletal muscle cells and leads to the contractures experienced by the patient early in an attack. 4. Prolonged depolarization of the muscle cell plasma membrane will lead to voltage inactivation of Na+ channels in the membrane, which will result in the muscle cell's being unable to fire an action potential. This is believed to be the cause of the paralytic phase of an attack and is supported by the observation that during the paralytic phase, the patient's skeletal muscle cells may be electrically inexcitable. 5. Insulin immediately and powerfully promotes the uptake of K+ by cells and the extrusion of Na+ from cells. Administration of insulin thus corrects the hyperkalemia, restores cellular K+ levels toward normal, and causes the resting membrane potential for the affected skeletal muscle cells to become closer to the normal resting value. In this way insulin is believed to terminate an attack of contractures or paralysis in these patients. 6. Long-term administration of salbutamol, a β2-agonist, increases the activity of the Na+, K+-ATPase in skeletal muscle cells. In this way, salbutamol administration leads to increased sequestration of K+ in muscle cells. Apparently this helps to prevent the K+ efflux that underlies episodes of hyperkalemia with resultant contractures that may be followed by periods of paralysis