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L J MULLINS

Publications and source records attributed to L J MULLINS.

18 recordsLinked to original sources

THE CONTROL OF THE MEMBRANE POTENTIAL OF MUSCLE FIBERS BY THE SODIUM PUMP.

Frog sartorius muscles were made Na-rich by immersion in K-free sulfate Ringer's solution in the cold. The muscles were then loaded with Na(24) and the extracellular space cleared of radioactivity. When such Na-rich muscles were transferred to lithium sulfate Ringer's solution at 20 degrees C, Na efflux was observed to increase with time, to reach a maximum about 15 minutes after the transfer of the muscles to Li(2)SO(4), and then to decline. The decline in efflux from these muscles was proportional to ([Na](i))(8) over a considerable range of [Na](i). The membrane potential of Na-rich muscles was about -48 mv in K-free sulfate Ringer's at 4 degrees C but changed to -76 mv in the same solution at 20 degrees C and to -98 mv in Li(2)SO(4) Ringer's at 20 degrees C. By contrast, muscles with a normal [Na](i) showed a fall in membrane potential when transferred from K-free sulfate Ringer's to Li(2)SO(4) Ringer's solution. The general conclusions from this study are (a) that Na extrusion is capable of generating an electrical potential, and (b) that increases in [Na](i) lead to reversible increases in P(Na) of muscle fibers.

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The concentration dependence of sodium efflux from muscle.

Frog sartorius muscles subjected to overnight loading with Na(+) in K-free Ringer in the cold were subsequently labeled with Na(24) and then immersed in choline Ringer and the efflux of Na(24) followed for 4 hours. The initial efflux of Na(+) appeared to be 17 pmole/cm(2) sec.; this value was maintained for 20 minutes and was followed by an abrupt decline to about 9 pmole/cm(2) sec. This latter rate was maintained for the next 20 minutes of efflux. The efflux then declined gradually with time and reached values of the order of 0.1 pmole/cm(2) sec. The back addition of counts lost from muscles enabled one to calculate the relationship between efflux and [Na](i) for muscle. This roughly approximates an S-shaped curve with a value at half-saturation of about 17 mmole Na per liter of fiber water. The efflux-concentration curve is closely described by assuming that 3 Na(+) are transported per carrier cycle.

Animals↗

THE INFLUENCE OF SODIUM-FREE SOLUTIONS ON THE MEMBRANE POTENTIAL OF FROG MUSCLE FIBERS.

The membrane potential of frog sartorius muscle fibers in a Cl- and Na-free Ringer's solution when sucrose replaces NaCl is about the same as that in normal Ringer's solution. The K(+) efflux is also about the same in the two solutions but muscles lose K and PO(4) in sucrose Ringer's solutions. The membrane potential in sucrose Ringer's solution is equal to that given by the Nernst equation for a K(+) electrode, when corrections are made for the activity coefficients for K(+) inside and outside the fiber. For a muscle in normal Ringer's solution, the measured membrane potential is within a few millivolts of E(K). This finding is incompatible with a 1:1 coupled Na-K pump. It is consistent with either no coupling of Na efflux to K influx, or a coupling ratio of 3 or greater.

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Sodium and potassium ion effluxes from squid axons under voltage clamp conditions.

Squid giant axons loaded with Na(24) were subjected to short duration (0.5 msec.) clamped depolarizations of about 100 mv at frequencies of 20/sec. and 60/sec. while in choline sea water. Under such conditions the early outward current was just about maximal at the time of termination of the clamping pulse. An integration of the early current versus time record gave 1.2 mucoulomb/cm(2) pulse, while a measurement of the extra Na(24) efflux resulting from repetitive pulsing gave a charge transfer of 1.4 mucoulomb/cm(2) pulse. In sodium-containing sea water and with pulses 50-75 mv more positive than E(Na) the Na(24) efflux is about 3 times the measured charge transfer. The efflux of K(42) from a previously loaded axon into normal sea water is only 50 per cent of the measured charge transfer when the membrane is held for about 5 msec. at a potential such that there is no early current, and such pulses are at 10-20/sec. The experiments appear to confirm the suggestion that the early current during bioelectric activity is sodium but provide unsatisfactory support for the identification of the delayed but sustained current solely with potassium ions. Resting Na(+) efflux is 0.6 pmole/cm(2) sec. mmole [Na](1), while the apparent K(+) efflux is about 250 pmole/cm(2) sec. and is little affected by hyperpolarization.

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The movement of thallium ions in muscle.

Measurements have been made of the fluxes of thallous ions (Tl(+)) across the membrane of frog sartorius muscle fibers. These show that at an external concentration of 74 microM the influx is about 270 x 10(-15) moles/cm.(2) sec., while the efflux from a muscle with an internal concentration equal to the above is 5 x 10(-15) moles/cm.(2) sec. The efflux is increased of the order of 300-fold during a muscle twitch, and Tl(+) reach a steady-state distribution between fiber water and Ringer solution that is very close to the corresponding ratio for K(+). High concentrations of Tl(+) depolarize the membrane about 58 mv. for a tenfold increase in external concentration. The results obtained are consistent with the view that the muscle fiber membrane cannot distinguish between the toxic heavy metal Tl(+) and K(+), provided that the concentrations of the former ion are kept low. High concentrations of Tl(+), if allowed to act for an appreciable period of time, lead to irreversible damage to muscle.

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An analysis of conductance changes in squid axon.

The membrane of the squid axon is considered on the basis of a pore model in which the distribution of the pore sizes strongly favors K(+) transfer when there is no potential. Electrical asymmetry causes non-penetrating ions on the membrane capacitor to exert a mechanical force on both membrane surfaces and this force results in a deformation of the membrane pore system such that it assumes a distribution of sizes favoring the ions exerting mechanical force. The ions involved appear to be Ca(++) on the outside of the membrane and isethionate(-), (i(-)) on the inside; as Ca(++) is equivalent in size to Na(+), the charged membrane is potentially able to transfer Na(+), when the ions deforming the membrane pore distribution are removed. A depolarization of the membrane leads to an opening of pores that will allow Na(+) penetration and a release of the membrane from deformation. The pores revert to the zero-potential pore size distribution hence the Na permeability change is a transient. Calculation shows that the potassium conductance vs. displacement of membrane potential curve for the squid axon and the "inactivation" function, h, can be obtained directly from the assumed membrane distortion without the introduction of arbitrary parameters. The sodium conductance, because it is a transient, requires assumptions about the time constants with which ions unblock pores at the outside and the inside of the membrane.

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Oscillatory behavior of the squid axon membrane potential.

Squid axons impaled with a microelectrode have been treated with concentrations of xylene and benzene such that there is no change in threshold or resting potential at 20 degrees C., while the spike height declines about 10 mv. A decrease in ambient temperature results in large, reversible, increases in threshold. While neither low temperature nor the added blocking agent induces repetitive firing from a single stimulus, the two treatments when combined do yield repetitive responses which commence at a sharply defined temperature. The alteration in the membrane responsible for the effects observed can be described by saying that there has been a large increase in the inductance of the equivalent electric circuit, and the temperature coefficient of the apparent membrane inductance has a Q(10) = 5.

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