Impairment of skeletal muscle adenosine triphosphate–sensitive K+ channels in patients with hypokalemic periodic paralysis
Domenico Tricarico, … , Karin Jurkat-Rott, Diana Conte Camerino
Domenico Tricarico, … , Karin Jurkat-Rott, Diana Conte Camerino
Published March 1, 1999
Citation Information: J Clin Invest. 1999;103(5):675-682. https://doi.org/10.1172/JCI4552.
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Article

Impairment of skeletal muscle adenosine triphosphate–sensitive K+ channels in patients with hypokalemic periodic paralysis

Abstract

The adenosine triphosphate (ATP)–sensitive K+ (KATP) channel is the most abundant K+ channel active in the skeletal muscle fibers of humans and animals. In the present work, we demonstrate the involvement of the muscular KATP channel in a skeletal muscle disorder known as hypokalemic periodic paralysis (HOPP), which is caused by mutations of the dihydropyridine receptor of the Ca2+ channel. Muscle biopsies excised from three patients with HOPP carrying the R528H mutation of the dihydropyridine receptor showed a reduced sarcolemma KATP current that was not stimulated by magnesium adenosine diphosphate (MgADP; 50–100 μM) and was partially restored by cromakalim. In contrast, large KATP currents stimulated by MgADP were recorded in the healthy subjects. At channel level, an abnormal KATP channel showing several subconductance states was detected in the patients with HOPP. None of these were surveyed in the healthy subjects. Transitions of the KATP channel between subconductance states were also observed after in vitro incubation of the rat muscle with low-K+ solution. The lack of the sarcolemma KATP current observed in these patients explains the symptoms of the disease, i.e., hypokalemia, depolarization of the fibers, and possibly the paralysis following insulin administration.

Authors

Domenico Tricarico, Serenella Servidei, Pietro Tonali, Karin Jurkat-Rott, Diana Conte Camerino

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Figure 1

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Digital average of the sarcolemma KATP currents of patients with HOPP an...
Digital average of the sarcolemma KATP currents of patients with HOPP and healthy subjects. KATP currents of the 18-year-old boy with HOPP (seven macropatches) (a) and of the 40-year-old woman with HOPP (14 macropatches) are shown (b). MgADP at 50 μM concentration failed to stimulate the current, whereas at 100 μM, current was reduced. In both patients with HOPP, MgATP (500 μM) completely reduced the currents. KATP currents of the 17-year-old healthy boy (eight macropatches) (c) and 40-year-old healthy woman (seven macropatches) are shown (d). In contrast to the patients with HOPP, in the healthy subjects large KATP currents were recorded that were stimulated by MgADP (100 μM) and completely reduced by MgATP (500 μM). HOPP, hypokalemic periodic paralysis; KATP, adenosine triphosphate–sensitive K+ channel; MgADP, magnesium adenosine diphosphate; MgATP, magnesium adenosine triphosphate.