In vivo assessment of interictal sarcolemmal membrane properties in hypokalaemic and hyperkalaemic periodic paralysis. Issue 4 (April 2020)

• Record Type: Journal Article
• Authors: Tan, S. Veronica; Suetterlin, Karen; Männikkö, Roope; Matthews, Emma; Hanna, Michael G.; Bostock, Hugh
• Is Part Of: Clinical neurophysiology. Volume 131:Issue 4(2020:Apr.)
• Page Start: 816
• Page End: 827
• Publication Date: 2020-04
• Subjects: Periodic paralysis -- Sodium channel -- Calcium channel -- Muscle excitability -- Membrane potential -- Paramyotonia congenita; AP action potential -- ATS Andersen-Tawil Syndrome -- CMAP compound muscle action potential -- ESN early supernormality (largest percentage decrease in latency for ISIs below 15 ms) -- ESN@ interstimulus interval for maximum ESN -- 5ESN early supernormality after 5 conditioning stimuli -- HypoPP Hypokalaemic periodic paralysis -- HyperPP Hyperkalaemic periodic paralysis -- ISI inter-stimulus interval -- Lat(15 Hz)First % change in latency for first muscle action potential of 15-Hz train -- Lat(15 Hz)Last % change in latency for last muscle action potential of 15-Hz train -- Lat(30 Hz)First % change in latency for first muscle action potential of 30-Hz train -- Lat(30 Hz)Last % change in latency for last muscle action potential of 30-Hz train -- LET long exercise test -- LSN late supernormality (mean percentage decrease in latency for ISIs between 50 and 150 ms) -- 2XLSN extra supernormality after 2 conditioning stimuli compared with 1 conditioning stimulus -- 5XLSN extra supernormality after 5 conditioning stimuli compared with 1 conditioning stimulus -- MC Myotonia Congenita -- MRRP muscle relative refractory period -- MSN mean supernormality (average latency reduction between MRRP and 1 sec, corresponding to area under curve when plotted with linear ISI axis -- 2XMSN extra mean supernormality after 2 conditioning stimuli -- 5XMSN extra mean supernormality after 5 conditioning stimuli -- MPkf(20 Hz C4+5) % change in amplitude for the first in train during the 4th and 5th cycle of 20 Hz repetitive stimulation -- MSuperN(20 HzBline) baseline early supernomality before the start of the 20 Hz trains. -- MVRC muscle velocity recovery cycle -- NC normal controls -- Pk(30 Hz)Last peak amplitude for last action potential in 30 Hz train as percentage of baseline -- Pk(30 Hz+30 s) peak amplitude 30s after end of 30-Hz train as percentage of baseline -- PMC paramyotonia congenita -- RSN residual supernormality (mean percentage decrease in latency at the end of the sweep, averaged for ISIs of 900 and 1000 ms -- 5XRSN extra residual supernormality after 5 conditioning stimuli -- SCM sodium channel myotonia -- TA tibialis anterior; Neurophysiology -- Periodicals; Electroencephalography -- Periodicals; Electromyography -- Periodicals; Neurology -- Periodicals; 612.8
• DOI: 10.1016/j.clinph.2019.12.414
• Languages: English
• ISSNs: 1388-2457

Abstract

Highlights: The muscle resting membrane potential is depolarised in HypoPP, but mostly normal in HyperPP. Muscle excitability studies support the presence of a window current in HyperPP. Excitability measures distinguish between HypoPP and HyperPP, and HyperPP and paramyotonia congenita. Abstract: Objective: Hypokalaemic periodic paralysis (HypoPP) is caused by mutations of Cav 1.1, and Nav 1.4 which result in an aberrant gating pore current. Hyperkalaemic periodic paralysis (HyperPP) is due to a gain-of-function mutation of the main alpha pore of Nav 1.4. This study used muscle velocity recovery cycles (MVRCs) to investigate changes in interictal muscle membrane properties in vivo . Methods: MVRCs and responses to trains of stimuli were recorded in tibialis anterior and compared in patients with HyperPP( n = 7), HypoPP ( n = 10), and normal controls ( n = 26). Results: Muscle relative refractory period was increased, and early supernormality reduced in HypoPP, consistent with depolarisation of the interictal resting membrane potential. In HyperPP the mean supernormality and residual supernormality to multiple conditioning stimuli were increased, consistent with increased inward sodium current and delayed repolarisation, predisposing to spontaneous myotonic discharges. Conclusions: The in vivo findings suggest the interictal resting membrane potential is depolarized in HypoPP, and mostly normal in HyperPP. The MVRC findings in HyperPP are consistent with presence of a window current, previously proposed on the basis of in vitro expression studies. Although clinically similar, HyperPP was electrophysiologically distinct from paramyotonia congenita. Significance: MVRCs provide important in vivo data that complements expression studies of ion channel mutations.