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Biomedical subjects

D D Koblin

Publications and source records attributed to D D Koblin.

82 records · Page 5Linked to original sources

Withdrawal convulsions in mice following nitrous oxide.

Mice may be induced to convulse after (but not prior to) breathing nitrous oxide. We found that the incidence of this withdrawal phenomenon is related to the partial pressure of nitrous oxide. A minimum (threshold) value of about 0.5 atm is necessary and the majority of mice convulse following exposure to 0.9 atm or greater. Exposures of longer than 15 to 30 minutes do not significantly increase the incidence of convulsions at any given partial pressure. The mice remain susceptible to the induction of convulsions for only a brief period after removal from nitrous oxide. Although the duration of susceptibility is slightly increased after exposure to higher partial pressures, susceptibility in almost all cases is lost by 90 minutes. In mice, exposure to nitrous oxide is associated with evidence of physical dependence as evidenced by withdrawal symptoms, symptoms that be related to the appearance of excitement which sometimes follows nitrous oxide anesthesia.

Animals↗

Mice tolerant to nitrous oxide are also tolerant to alcohol.

Mice exposed to 50% nitrous oxide for 3 weeks become tolerant to nitrous oxide. The nitrous oxide-tolerant animals are also tolerant to ethanol, as measured by a 40% decrease in ethanol-induced sleep times and 15% higher blood alcohol levels upon awakening compared to control mice raised in air. These results suggest a common mechanism for the development of tolerance to both alcohol and nitrous oxide.

Animals↗

Tolerance of mice to nitrous oxide.

Mice continuously exposed to a subanesthetic dose of nitrous oxide (N2O) become tolerant to nitrous oxide, as measured by an increase in their ED50 (dose required to abolish the righting reflex in 50% of animals) for N2O. The maximum increase in ED50 is approximately 0.25 atm for mice exposed to 40, 50 or 70% N2O for 2 to 3 weeks. Mice exposed to 25% N2O for 3 weeks do not develop tolerance. Mice exhibit a withdrawal syndrome when removed from the subanesthetic environment after exposure to 40 to 70% but not 25% N2O for 3 weeks. Tolerance to 50 or 70% N2O develops within 1 week and is maximal at 2 weeks. Tolerance to nitrous oxide is lost within 6 days following removal of the animals from the subanesthetic environment. Synaptic membrane fatty acid, phospholipid, and cholesterol compositions of tolerant animals are not significantly altered.

Acetylcholinesterase↗

Role of voltage-sensitive receptors in nicotinic transmission.

This paper compares the conductance induced by bath-applied acetyl-choline (ACh) and by the same transmitter released from nerve terminals at Electrophorus electroplaques. For the former case, dose-response relations are characterized by the maximal agonist-induced conductance, rgamma (130 mmho/cm2), and by the concentration which induces half this conductance; this concentration is termed Kapp and equals 50 micron at -85 mV. For the latter case, neurally evoked postsynaptic currents (PSCs) are characterized by the peak conductance during strongly facilitated release, gPSC, and by the rate constant for decay, alpha. Since gPSC roughly equals rgamma, it is concluded that the PSC activates nearly all available receptor channels. These and other data agree with recent estimates that during the growth phase of the quantal response, (a) the ACh concentration is at least several hundred micromolar; and (b) most nearby channels are activated. However both alpha and Kapp increase during depolarization, at a rate of about e-fold per 86 mV. These observations on voltage sensitivity suggest that a suprathreshold synaptic event is rapidly terminated because the action potential abruptly releases ACh molecules from receptors.

Acetylcholine↗