Zusammen/assung. All verkiirzten Purkinje-F~den wurden die lV[embranpotentiale miter Spannungsklemmbedingungen ge~ndert. Die Membran wurde sprunghaft oder mit konstanter Geschwindigkeit de-und repolarisiert. Bei Depolarisation erscheint bei --20 mV ein positivcr (Ausw~rts-) Strom, der bei Depolarisation zu positiveren Membranpotentialen gr58er wird. Der positive Strom erreicht sein Maximum etwa 20 ms nach Beginn der Depolarisation, und wird mit einer Zeitkonstante yon ca. 50 ms inaktiviert. Wird unmittelbar naeh der Depolarisation die )llembran repolarisiert, so ist der positive Strom yon dieser Riehtungs~nderung nicht beeinfiui3t. Auch wghrend der Repolarisation zeigt er eine ~hnliche Potential-und Zeitabh£ngigkeit wie bei Depolarisation.Der positive Strom ist unabh.ingig yon der extracellul£ren Natrium-oder Kalium-Konzentration. Sowohl in natriumhaltiger als aueh natriumfreier LSsung ist der positive Strom stark vermindert, wenn das extracellu]i~re Chlorid durch ein gering permeirendes Anion ersetzt wird. Hieraus wird geschlossen, dab bei Depolarisation bei --20 mV und positiveren Membranpotentialen ein zeitabh~ngiger Chloridstrom ausgel6st wird. Bei negativeren ~embranpotentiMen ist der Chloridstrom klein.Es wird gezeigt, dab der positive Chloridstrom ffir die schnelle Phase der Repolarisation yon der Spitze des Aktionspotentials zum Plateau verantwortlich ist.In Priiparaten, die in chloriclfreier LSsung gehalten wurden, ist der erregende lqatriumstrom bei Depolarisation vergrSl~ert.Summary. In short Purkinje fibers the membrane potential was changed by a voltage clamp technique. The membrane was de-and repolarized using voltage steps or voltage changes at constant speeds. On depolarization from the resting potential, at --20 mV a positive (outward) current component appears which increases at more positive potentials. The peak of the positive current is delayed by about 20 ms relative to the start of the depolarization. The positive current is inactivated with time constant of 50 ms. Time and voltage dependence of the positive current seem to be independent of the direction of potentiM change.The positive current is not affected by removal of extracelhlar sodium or potassium. In the absence as welt as in the presence of sodium, removal of extracellular chloride markedly reduces the positive current. It is concluded that a time dependent chloride current is triggered above --20 inV. At more negative membrane potentials the chloride current is small. The positive chloride current is shown to be responsible for the early rapid repolarization from the crest of the spike to the plateau of the action potential Preparations kept in chloride-free solutions display an increased excitatory sodium current during depolarization. * This work was supported by the "Deutsche Forschungsgemeinschaft." 15 Pflfigers Arch. ges. Physiol., Bd. 295

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SUMMARY1. Quantitative ionophoresis at the neuromuscular junction is possible when (a) the drug is released from appropriate distances (15-20 jm for most drugs), (b) the topology of receptors is known and (c) high resistance drug pipettes (100-200 MO) are used.2. With this method, drug concentration-endplate conductance relations were determined in voltage-clamped end-plates of the frog for the agonists ACh, carbamylcholine (CCh) and suberyldicholine (SubCh).3. Based on the co-operative and independent model, theoretical dose-response curves were computed using as parameters the Hill coefficient nH, maximum conductance gmax.. and apparent dissociation constant K. It was found that the co-operative model fitted the data much better than the independent model. 4. Based on the co-operative model, the mean maximum conductance for ACh was gmax. 169 nS/sm, equivalent to 9000 ionic channels/,sm length of a nerve terminal which can be opened at high drug concentrations.5. The maximum conductance for CCh at -80 mV membrane potential was, on the average, 78 % of that for ACh measured at the same end-plates. This value is termed the relative efficacy of CCh. 6. The mean values for the apparent dissociation constant K were 27*8 /SM for ACh, 336 ,um for CCh and 18 ,uM for SubCh.7. The inhibition of the acetylcholinesterase activity by edrophonium (3-10 ,lM) affected only the local ACh concentration at the receptor sites, but not gmax. and nH.8. Dose-response curves measured before and after removal ofsingle nerve terminals in collagenase-treated muscle fibres showed no change in the nH, gmax. and K.A slight increase in gmax. to a value of 218 nS//,m was observed comparing collagenase-treated and untreated end-plates.9. Desensitization of receptors may occur in the range of several tens of milliseconds.

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