Ionchannelopathy__培训课件.pptVIP

人：ClC-Ka，ClC-Kb（突变引起Barter综合征，大量盐分丧失） 鼠：ClC-K1（缺失引起小鼠肾原性尿崩症）， ClC-K2 * Episodic Ataxia(阵发性共济失调） An autosomal dominant disorder characterized by sporadic bouts of ataxia (severe discoordination) with or without myokymia (continuous muscle movement, 肌纤维颤动) * KCNA1: Encodes Kv1.1. Expressed in basket cells and interneurons that form GABAergic synapses on Purkinje cells. Aid in the repolarization phase of action potentials, thus affecting inhibitory input into Purkinje cells and, thereby, all motor output from the cerebellum. * Calcium channelopathies Hypokalemic periodic paralysis Familial hemiplegic migraine Episodic ataxia type II Spinocerebellar ataxia VI * Hypokalemic periodic paralysis（低钾性周期性麻痹） Muscle weakness or paralysis with a matching fall in potassium levels in the blood Triggered by strenuous exercise followed by rest, high carbohydrate meals, meals with high sodium content, sudden changes in temperature, and even excitement, noise or flashing lights * CACNA1S (Cav1.1) mutations: loss-of-function mutation, cannot open normally. the channel has a reduced excitability and signals from CNS are unable to depolarize the muscle——paralysis. low extracellular K+ concentration will cause the muscle to repolarize to the resting potential more quickly. It becomes more difficult to reach the calcium threshold at which the muscle can contract, and even if this is reached then the muscle is more likely to relax. * Treatment Avoiding carbohydrate-rich meals, strenuous exercise and other identified triggers acetazolamide (Diamox) or another carbonic anhydrase inhibitor，potassium-sparing diuretics such as spironolactone. drinking KCl dissolved in water. * Familial hemiplegic migraine（家族性偏瘫性偏头痛） An autosomal dominant classical migraine subtype that typically includes hemiparesis (weakness of half the body) during the aura phase. It can be accompanied by other symptoms, such as ataxia, coma and epileptic seizures CACNL1A4：P/Q-type calcium chann