In vivo assessment of muscle membrane properties in myotonic dystrophy

Abstract

Introduction Myotonia in myotonic dystrophy types 1 (DM1) and 2 (DM2) is generally attributed to reduced chloride channel conductance. We used muscle velocity recovery cycles (MVRCs) to investigate muscle membrane properties in DM1 and DM2, with comparisons with myotonia congenita (MC). Methods MVRCs and responses to repetitive stimulation were compared between patients with DM1 (n=18), DM2 (n=5), MC (n=18), and normal controls (n=20). Results Both DM1 and DM2 showed enhanced late supernormality after multiple conditioning stimuli, indicating delayed repolarization as in MC. Contrary to MC, however, DM1 showed reduced early supernormality after multiple conditioning stimuli, and weak DM1 patients also showed abnormally slow latency recovery after repetitive stimulation. Discussion These findings support impaired chloride conductance in both DM1 and DM2. The early supernormality changes indicate that sodium currents were reduced in DM1, while the weakness-associated slow recovery after repetitive stimulation may provide an indication of reduced Na+/K+-ATPase activation.

In vivo assessment of muscle membrane properties in the sodium channel myotonias

“…The recording technique was performed as described previously for tibialis anterior (TA) and is briefly summarized below. For details of the MVRC and ramp protocols see Tan et al .…”

“…MVRCs, consisting of MRRP, ESN and LSN, can be reliably measured in human muscles by direct stimulation and recording of a bundle of adjacent muscle fibers with a sequence of paired electrical pulses of equal amplitude and varying interstimulus interval (ISI) . They indicate a rapid onset of membrane depolarization during limb ischemia and have been used to infer muscle membrane depolarization in renal failure and to provide information about membrane abnormalities in critical illness myopathy, Andersen‐Tawil syndrome, myotonia congenital (MC), and myotonic dystrophy …”

Sarcolemmal excitability in the myotonic dystrophies

“…However, Tan et al . recently concluded that Na + /K + pump dysfunction is also implicated in DM1 (but not in DM2) from insights gained in muscle excitability using a recently developed in vivo technique, multifiber muscle velocity recovery cycle (MVRC) assessment of a cohort of patients with DM1.…”

“…We also expected that such dysfunction would be likely to manifest as evidence of depolarization of the resting muscle membrane potential (RMMP) in more severely affected individuals due to loss of its electrogenic function. The current study tested for this by using MVRCs, a technique already used to study a number of acquired and inherited conditions of skeletal muscle …”

Sarcolemmal excitability attributes of the myotonic dystrophies as assessed by muscle velocity recovery cycles (mvrcs)

“…Muscle velocity recovery cycle (MVRCs) assessment represents a new automated technique whereby muscle membrane polarisation properties can be quantitated in vivo. The study aim was to characterise the excitability attributes of DM1 and DM2 comparing with that of normal control subjects and the results of a recently published myotonic dystrophy cohort using the same technique 1 .…”