How hypokalemia worsens LQTS

How hypokalemia worsens LQTS

How hypokalemia worsens LQTS: Hypokalemia is an important and common risk factor in drug induced LQTS. Low extracellular potassium paradoxically reduces I_Kr, the rapid component of delayed rectifier potassium current by enhanced inactivation. As a result, hypokalemia prolongs the QT interval.

It is well known that hypokalemia worsens the effect of both congenital and drug-induced long QT syndrome. An experimental study by Jun Guo, Hamid Massaeli, Jianmin Xu, Zongchao Jia, Jeffrey T Wigle, Nasrin Mesaeli and Shetuan Zhang [1] documented that I_Kr channel (rapid component of delayed rectifier potassium current – mediated by KCNH2 gene) is controlled by extracellular potassium concentration. Lowering extracellular potassium ion concentration accelerates the internalization and degradation of I_Kr channels [2,3]. Exaggerated competitive block by sodium can also contribute [2,4].

There is no change in Kv1.5 (I_Kur – ultra-rapid delayed rectifier potassium current) with a decreased extracellular potassium concentration. At the same time a modest reduction (30.3%) in KvLQT1 (I_Ks – slow component of delayed rectifier potassium current) was noted.

References

1. Jun Guo, Hamid Massaeli, Jianmin Xu, Zongchao Jia, Jeffrey T Wigle, Nasrin Mesaeli, Shetuan Zhang. Extracellular K⁺ concentration controls cell surface density of I_Kr in rabbit hearts and of the HERG channel in human cell lines. J Clin Invest. 2009 Sep;119(9):2745-57.
2. Eleftherios M Kallergis, Christos A Goudis, Emmanuel N Simantirakis, George E Kochiadakis, Panos E Vardas. Mechanisms, risk factors, and management of acquired long QT syndrome: a comprehensive review. ScientificWorldJournal. 2012;2012:212178.
3. T Yang, D J Snyders, D M Roden. Rapid inactivation determines the rectification and [K+]o dependence of the rapid component of the delayed rectifier K+ current in cardiac cells. Circ Res. 1997 Jun;80(6):782-9.
4. H Numaguchi, J P Johnson Jr, C I Petersen, J R Balser. A sensitive mechanism for cation modulation of potassium current. Nat Neurosci. 2000 May;3(5):429-30.