Fig. 5. Isoflurane decreases the response to acetylcholine of α4β2acetylcholine receptors expressed in Xenopus  oocytes. (A ) Fractional decrease in a single preparation. The shallowness of the isoflurane concentration–effect curve (Rγ slightly more than 1) bears no necessary relation to the steepness (Pγ) of the population concentration–effect relation that the receptor may mediate. Assuming, for example, that anything less than a 50% (0.5 fraction) depression allows movement in response to incision and that more than 50% prevents movement, the resulting population concentration–effect relation is infinitely steep (D ; the relation is approximated by a curve with a Pγ of 100). But if receptors differ among humans and if the boundary between movement–no movement remains at 50%, then the population concentration–effect relation becomes less steep (B ). At concentration A in (B ), 100% of patients would move with incision; at B, 67% would move; at C, 33%; and at D, none would move. Although the resulting concentration–effect curve (D ) is steep (Pγ of 10, a value found in MAC studies, see fig. 1), it is not infinitely steep. If the receptor concentration–effect curves are distributed more broadly [C ; points A, B, C, and D have the same meaning as in (B )], the resulting population concentration–effect curve is still less steep (Pγ 2.5) (D ). The points (diamonds, triangles, and circles) were obtained by calculating the fraction of patients that would be immobile at 10, 20, 30, 40, etc. μm isoflurane.

Fig. 5. Isoflurane decreases the response to acetylcholine of α4β2acetylcholine receptors expressed in Xenopus  oocytes. (A ) Fractional decrease in a single preparation. The shallowness of the isoflurane concentration–effect curve (Rγ slightly more than 1) bears no necessary relation to the steepness (Pγ) of the population concentration–effect relation that the receptor may mediate. Assuming, for example, that anything less than a 50% (0.5 fraction) depression allows movement in response to incision and that more than 50% prevents movement, the resulting population concentration–effect relation is infinitely steep (D ; the relation is approximated by a curve with a Pγ of 100). But if receptors differ among humans and if the boundary between movement–no movement remains at 50%, then the population concentration–effect relation becomes less steep (B ). At concentration A in (B ), 100% of patients would move with incision; at B, 67% would move; at C, 33%; and at D, none would move. Although the resulting concentration–effect curve (D ) is steep (Pγ of 10, a value found in MAC studies, see fig. 1), it is not infinitely steep. If the receptor concentration–effect curves are distributed more broadly [C ; points A, B, C, and D have the same meaning as in (B )], the resulting population concentration–effect curve is still less steep (Pγ 2.5) (D ). The points (diamonds, triangles, and circles) were obtained by calculating the fraction of patients that would be immobile at 10, 20, 30, 40, etc. μm isoflurane.

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