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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

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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 5

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In vitro effects of low-K+ solution and different concentrations of free...
In vitro effects of low-K+ solution and different concentrations of free Ca2+ ion on KATP channel. The muscle fibers were preincubated for 80 min with low-K+ solution (open bars) or with normokalemic solution (closed bars) before recordings. A linear relationship between the number of levels of the KATP channels vs. the corresponding amplitude in the absence (closed circles), or in the presence, of 8 μM (open circles) and 16 μM (open triangle) concentrations of free Ca2+ ion (a) was found. Fraction of time spent in open state by each subconductance level in the absence (b) or in the presence of 8 μM (c) and 16 μM (d) concentrations of free Ca2+ ion (a). Only after incubation of the muscle with the low-K+ solution, the Ca2+ ion forced the channel into the subconductance states, reducing the open probability of the O4 level and increasing the open probability of the sublevels.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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