Decrease In Resting Membrane Potential Research Articles

Characterization of neuromuscular transmission in mice with progressive motoneuronopathy

Progressive motoneuronopathy (PMN) is an autosomal recessive mouse disease, which is characterized by the development of hind limbs paralysis rapidly progressing to the anterior parts of the body, muscular atrophy, respiratory depression, and death at 6-7 postnatal weeks. Here, we recorded the resting membrane potential (RMP), spontaneous miniature endplate potentials (MEPPs), and quantum content of endplate potentials (EPP) at the diaphragm muscle fibers in controls and PMN mice aged 18 to 43 days. In control animals, there was a progressive increase in RMP, MEPP frequency and EPP quantum content, as well as a decrease in mean MEPP amplitude. In PMN mice, the developmental increase in frequency and decrease in the amplitude of MEPPs was practically stopped at the postnatal day 18, whereas RMP increased but only until the age of 31 days and then progressively decreased. The distribution histogram of RMP in PMN mice older than 35 days revealed the existence of two subpopulations of muscle fibers: one showing a denervation-like decrease in RMP and the second, which was matching controls. In addition, EPP quantum content was significantly attenuated in older PMN animals. These results indicate that neurotransmission is severely affected in advanced, but not in early stage of disease, which is apparently due to a partial denervation of the muscles.

Denervation and the time course of resting membrane potential changes in skeletal muscle in vivo

The effect of denervation on the skeletal muscle resting membrane potential (RMP) was studied in the soleus muscle of the intact rat. The RMP decreased much later than reported in previous in vitro studies. With a very short nerve stump (less than 2 mm), the RMP began to decrease 18 h after denervation and 4 h after miniature end-plate potentials ceased. With a longer nerve stump (39 to 43 mm) the decrease in RMP was delayed about 3 h. Our findings in vivo fail to confirm previous arguments against a role for acetylcholine in regulating the muscle RMP. The influence of usage and the possible effects of spontaneous quantal and nonquantal acetylcholine release or other hypothetical factors are discussed.

The effect of septic shock on skeletal muscle action potentials in the primate.

Techniques developed for the in vivo study of cellular physiology have been applied to septic shock in primates. Measurements of skeletal muscle transmembrane resting and action potentials were correlated with an analysis of fluid and electrolyte changes in the intracellular and extracellular compartments of skeletal muscle. The data obtained indicated a marked depletion of muscle extracellular water and an increase in intracellular sodium chloride and water content during shock. The significant decrease of resting membrane potential was associated with a decrease in amplitude of the action potential and prolongation of both the repolarization and depolarization time. In addition, there was a decrease of muscle intracellular potassium concentration during shock. This study demonstrates that the alterations in cellular membranes in hemorrhagic shock and septic shock are similar.

Temperature effects on resting potential and spike parameters of cat motoneurons.

During intracellular recording from cat spinal motoneurons, the lumbo-sacral cord was subjected to rapid local temperature changes. Cooling to 30° C causes a decrease in the resting membrane potential (RMP), a transient increase in spike overshoot, and increases in the input resistance and the durations of both the action potential and the hyperpolarizing after-potential (HAP). Warming causes these membrane parameters to change in the opposite direction and can result in a failure of antidromic activation. The RMP changes are dependent upon the RMP at normal temperature, being negligible in cells having an initial RMP greater than 70 mV. The Q10-values of the three peaks of the differentiated spike are relatively high and nearly identical to the Q10-values of the corresponding rate constants for sodium activation and inactivation and potassium activation measured by Frankenhaeuser and Moore in toad nerve fibers, i.e. 1.71, 2.35 and 3.12, respectively. Delayed sodium inactivation and potassium activation explain the increase in spike overshoot observed during cooling, and the high Q10 of potassium activation is nearly identical to the Q10 of the time to peak of the HAP (3.12 vs. 2.97). The decrease in RMP during cooling is attributed to a decrease in the PK∶PNa ratio rather than to a blockage of an electrogenic sodium pump; the differences in RMP temperature sensitivities between cells with high and low initial RMP's might be due to a higher resting PK (anomalous rectification) at higher RMP. We conclude that the electrogenic pump does not normally contribute significantly to the RMP of cat motoneurons.

Early membrane depolarization of the fast mammalian muscle after denervation.

The first alteration noted after denervation of the extensor digitorum longus muscles of rats was a decrease in resting membrane potential (RMP) which occurred at about 2h. The exact time course of this membrane depolarization was dependent upon the intramuscular length of the degenerating nerve stump. The decrease in RMP occurred prior to any detectable alteration in adenosine triphosphate and phosphocreatine content of the muscle. Prior to failure of spontaneous transmitter release, which occurred 10 h after denervation, some muscle fibres showed an increase in frequency of the miniature end-plate potentials (m.e.p.p.) with no alterations in amplitude and shape of the single potentials. Appearance of areas sensitive to acetylcholine (ACh) on the extra-junctional membrane occurred at 24 h after crushing the motor nerve. At 48 h after denervation a high ACh-sensitivity appeared at the muscle-tendon region, but was not detected in the majority of the muscle fibres studied midway between end-plate region and muscle-tendon area. The transverse resistance of a unit area of the muscle membrane was increased 3 days after denervation. These results provide evidence that the processes of post-denervation changes occur in the following temporal sequence: a) partial depolarization of the postsynaptic muscle membrane; b) a decrease and subsequent cessation of the spontaneous transmitter release preceded in some fibres by a transient increase in m.e.p.p. frequency; c) appearance of extrajunctional ACh sensitivity; d) increase in the transverse resistance of a unit area of the muscle membrane. It is suggested that the motor nerve releases more than one neurotrophic substance.