Biomedical subjects

S Misler

Publications and source records attributed to S Misler.

40 records · Page 3Linked to original sources

PubMed1983

Post-tetanic potentiation of acetylcholine release at the frog neuromuscular junction develops after stimulation in Ca2+-free solutions.

At many synapses, previous activity increases the amount of transmitter released by a single action potential. This potentiation of transmitter release is usually attributed to the local accumulation of the calcium ions that cross the axolemma during an action potential. We found that potentiated transmitter release can be observed at frog neuromuscular junctions after periods of repetitive stimulation in Ca2+-free solutions, if Ca2+ is restored after the tetanus. Potentiation is greater and more prolonged, the lower the level of extracellular K+. This component of potentiation may be due to Ca2+ that accumulates within the terminal in exchange for intracellular Na+.

Acetylcholine↗

PubMed1983

Gating of ion channels made by a diphtheria toxin fragment in phospholipid bilayer membranes.

B45, a fragment containing the major hydrophobic region of diphtheria toxin, increases the conductance of thin lipid membranes by forming ion-conducting channels that are gated by transmembrane voltage, Vm, and the bath pH. Single-channel currents show "bursting" behavior in the form of rapid transitions between a closed and an open conductance level. The average duration of a current "burst," as well as the total time a channel is actually open within a burst, decreases with increasing Vm. Analysis of these data suggests that, over a range of Vm, increases in the rate constants for transitions from the open to the closed states largely account for the decline in macroscopic conductance with increasing Vm. Increases in rate constants for transitions from a closed to an open conductance state are more likely to account for the increase in macroscopic conductance with increasing bath pH. Since several diphtheria toxin fragments and mutants are currently available, each containing various portions of the B45 region, it may be possible to study the relationship of the structure of these complex proteins to the detailed gating properties of the ion channels that they form.

Diphtheria Toxin↗

PubMed1980

Tests of an electrostatic screening hypothesis of the inhibition of neurotransmitter release by cations at the frog neuromuscular junction.

We have investigated an electrostatic screening hypothesis of cationic inhibition of quantal release at the neuromuscular junction of the frog (Rana pipiens). According to this hypothesis, increasing the extracellular concentration of an inhibitory cation reduces the quantal content (m) of the end-plate potential by reducing the ability of negative surface charge to attract Ca2+ to the external surface of the presynaptic membrane. The inhibitory power of various cations should depend only on their net ionic charge and should increase strongly with increasing charge. We have demonstrated, in Ringer's solutions containing modified concentrations of Na+, Ca+, and Mg2+, that at fixed concentrations of Ca2+ and Na+ (a) the dependence of m on [Mg2+]0 is satisfactorily accounted for by electrostatic theory and (b) the dependence of m on the univalent cation concentration of the modified Ringer's solution is satisfactorily predicted from the Mg2+ inhibition of m. (Glucosamine or arginine was used to replace a fraction of the Na+ content of Ringer's solution in the latter experiments.) These results are consistent with electrostatic screening actions of Mg2+ and univalent cations in the inhibition of m. We have also re-examined the inhibition of m caused by the addition to Ringer's solution of two trace concentration divalent cations, Mn2+ and Sr2+. Our data suggest that the inhibition of m by Sr2+ at high quantal contents may also be due to surface charge screening, while the potent inhibitory actions of Mn2+ may be due to its ability to bind negative surface charge.

Animals↗

PubMed1979

Action of black widow spider venom on quantized release of acetylcholine at the frog neuromuscular junction: dependence upon external Mg2+.

Black widow spider (Latrodectus tredecimguttatus) venom (BWSV) increases several hundredfold the frequency of occurrance of minature end-plate potentials (Fmepp) at frog neuromuscular junctions bathed in Ringer's solutions containing either Ca2+ of Mg2+, but it has little effect on Fmepp at junctions bathed in modified Ringer's solution containing 1--2 mM ethylene glycol bis(beta-aminoethyl ether)-N,N'-tetraacetic acid (EGTA) but no Ca2+ or Mg2+. When Mg2+ is added to preparations that have been treated with BWSV in the modified solution, Fmepp increases exponentially with time. Fmepp falls again to low values when the Mg2+ is removed. The rate constant of the exponential rise is proportional to [Mg2+]o in the range 1--4 mM, and the threshold [Mg2+]o is 0.1--0.5 mM. Increasing the K+ concentration of the bathing solution decreases the ability of Mg2+ to increase Fmepp. Addition of Ca2+, Co2+, Mn2+, or Zn2+ also leads to a large increase in Fmepp. These results are consistent with the possibility that BWSV increases the permeability of the nerve terminal to divalent cations. BWSV can, however, increase Fmepp in hypertonic solutions in the absence of external divalent cations. This result suggests that the effects of BWSV on the nerve terminal may not be confined to increasing the permeability of the plasma-lemma.

Acetylcholine↗