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 2

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Sample traces of single sarcolemma KATP channel from two patients with H...
Sample traces of single sarcolemma KATP channel from two patients with HOPP and from a healthy subject. The KATP channel of the 40-year-old woman with HOPP (a) and of the 18-year-old boy with HOPP (b) transits through subconductance states of low open probability, all blocked by ATP. In the 17-year-old healthy boy, only one open level blocked by ATP is clearly visible (c). In the 40-year-old woman with HOPP, the O1 (open circles) and O2 (closed circles) levels had slope conductances of 25 pS and 32 pS at negative potentials, and 40 pS and 47 pS at positive potentials, respectively (d). In the 18-year-old boy with HOPP, the slope conductances of O1 (open circles), O2 (closed circles), and O4 (closed squares) levels were 27 pS, 35 pS, and 72 pS at negative potentials, and 40 pS, 47 pS, and 46 pS at positive potentials, respectively (e). In the 18-year-old healthy boy, the O4 level (closed squares) had a slope conductances of 72 pS and 45 pS at the negative and positive potentials, respectively (f).