Membrane potentials, current-voltage relationships, and contractile parameters were studied in intact muscle cell bundles obtained from two patients with adynamia episodica hereditaria. In a normal extracellular medium, the cell membranes had resting potentials of about -80 mV and their current-voltage relationships were not significantly different from control curves. In contrast to normal muscles the afflicted cells were paralyzed in a medium having 6-10 mmol/liter potassium. The mechanisms of paralysis in the two specimens were different from each other. Many fibers from one patient were spontaneously active even in normal solution. In high potassium solution spontaneous activity was increased and the cells gradually depolarized to values at which excitatory sodium current is normally inactivated. This depolarization was connected with an increased sodium conductance and was reversed by the application of tetrodotoxin (TTX). The fibers from the other patient were not spontaneously active. In high potassium solution they were paralyzed at membrane potential values at which normal fibers would still contract. The reason for this paralysis was a reduced excitability.

Three patients with paramyotonia congenita and 3 control persons were biopsied for an in vitro investigation of the sarcolemmal membrane parameters and of the contractile properties of paramyotonic muscle. At 37 degrees C, paramyotonic muscle fibers had normal resting potentials, but on cooling to 27 degrees C they depolarized. Depolarization to -60 mV caused spontaneous activity, and further depolarization to -40 mV caused inexcitability. Depolarization could be prevented by the application of tetrodotoxin, a finding suggesting a defect in the Na channels. Analysis of the membrane current densities using voltage clamps with 3 microelectrodes revealed that in paramyotonic patients at 37 degrees C all component conductances were normal, except for a decreased Cl conductance in the patient who had myotonia in a warm environment. At 27 degrees C, the Na and Cl conductances were abnormally high. The K conductance was always normal. The results explain the clinical symptoms of weakness and paralysis. Potassium- and caffeine-contracture experiments gave normal results. The clinical symptom of paramyotonic stiffness, therefore, has not been explained by these studies.

SUMMARY1. In frog skeletal muscle strontium can replace calcium in potassium contractures for 5 hr, though it is less effective than Ca. Sr can restore the responsiveness to K after it had been lost in the presence of Mn.2. Muscles refractory to caffeine following repeated exposure to it in the absence of Ca, recover in part following addition of Sr. 3. The uptake of 85Sr was increased during mechanical activity, whereas the uptake of 58Co was not changed. Resting uptake of 58Co was 3-4 times greater than that of 85Sr.4. Sr fully activated the myofibrillar adenosine triphosphatase (ATPase), though its affinity was about 30 times less than Ca.5. The sarcoplasmic reticulum took up Sr, though less effectively than Ca.

In a comprehensive experimental study, the influence of changes in extra-and intracellular pH on the mechanical and electrical activity of frog heart ventricle preparations has been investigated. The twitch tension and potassium contracture tension were decreased in acid solutions, provided that the concentration of calcium or the frequency of stimulation was low. In solutions with a high calcium concentration, prolonged exposure to acid leads to an increase of the potassium contractures. The electrical activity, measured by intracellular microelectrodes, is abolished in acid solutions if the change of solution in the extracellular space is enforced by perpendicular jet superfusion; with slow perfusion it is well maintained except when [Ca] is high. The lowering of intracellular pH by applying a solution saturated with 80% CO 2 while keeping the extracellular pH constant causes a rapid drop in twitch tension followed by partial recovery. The relaxation phase of single twitches is prolonged and potassium contractures are markedly increased after the high CO 2 has acted for several minutes. When both intra- and extracellular pH are decreased, both twitches and potassium contractures are markedly decreased. The electrical activity is maintained. Some of the effects of variations in pH are discussed in terms of changes in the processes of mechanical activation and inactivation.

The membrane conductance of rat muscles (mainly gastrocnemius (G) and soleus (S)) was measured by using the two-microelectrode technique and the current point clamp method. Thin muscle bundles were washed in Tris chloride and Tris propionate solutions containing 6 mM K. The current strength was always 5 x 10-9 A and the steady-state membrane voltage was about 5 mV. The average chloride conductance (gcl, in mumho/cm2) of normal muscles was 845 (G) and 1,025 (S). The potassium conductance (gk) was 99 (G) and 161 (s). In separate measurements, the contribution of the chloride conductance (gcl) to the total membrane conductance (gm) was 89% for normal G and S. Two weeks after denervation the average gcl decreased to 440 in G and 191 in S; gk increased to 205 in G and to 364 in S in the presence of 0.1 mM Ca in solution; the increase in gk was less when measurements were made in the presence of 3mM Ca and 1 mM Mg. The contribution of gcl to gm was 60% in G and 30% in S in 14-day denervated muscles. The coefficient of variation for gcl/gk in 30 normal and 46 denervated muscles was 0.91 and 0.46, respectively. The curve representing the voltage-current relationship of muscles washed in Cl-free solutions containing 60 mM K was S-shaped in normal and in denervated muscles, but the changes in slope were less marked in the latter.