Biomedical subjects
Publications and source records attributed to K Koketsu.
The ionic mechanism of the membrane outward current (ACh-current) of bullfrog atrium muscle, induced by acetylcholine in K-free solution, was analyzed by a voltage-clamp experiment. The results suggested that the ACh-current was induced not only by an increase in K-conductance but also by an activation of the electrogenic Na-pump.
The effect of adrenaline (Ad) on the electrogenic Na+ pump of bullfrog visceral nerve fibers was studied, by testing the effect of this drug on the K-activated hyperpolarization (KAH) of these nerve fibers. KAHs were recorded by adding K (0.2--5 mM) to an extracellular K-free solution with which preparations were previously perfused and the actual KAH amplitude (net KAH) was estimated by taking into account the amplitude of membrane depolarization induced by K in the presence of ouabain (0.001 mM). The dose-response relation between K concentrations and net KAHs follows Michaelis-Menten kinetics; the log dose-response relation showed a sigmoid curve and the Lineweaver-Burk Plot of dose-response relation showed a straight line when nH=1.3. The net KAH was augmeted by Ad (0.03--1 mM); facilitative effects of three kinds of catecholamine on the net KAH were Ad greater than noradrenaline greater than isopreterenol. The log dose-response curve was shifted to the left in parallel in the presence of Ad; the Lineweeather-Burk plot showed a straight line when nH=1.3 and this line met the control line at the ordinate point where K concentration is infinitive, while the apparent dissociation constant (Km) decreased to 0.82 from 1.3 mM (control) in the presence of 0.3 mM Ad. Net KAH was augmented by the removal of extracellular Cl or by the action of TEA; the membrane resistance was expected to increase under these experimental conditions. The dose-response relation obtained under these conditions showed an increase of maximum response without changes in Km value. It was concluded on the basis of the present results that the increase in net KAH by Ad was due to an increase in the electrogenic Na+ pump current. The mechanism underlying such an Ad action was discussed, and it was suggested that the rate of the electrogenic Na+ pump was increased by the action of Ad.
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Electrogenic Na+ pump currents during K+-activated hyperpolarizations of bullfrog atrium muscle fibres are increased by adrenaline. The log dose-response relation between these currents and activating K+ concentrations is expressed by a sigmoidal curve, which is shifted in parallel to the left by adrenaline. It is suggested that adrenaline increases the rate of Na+ extrusion without increasing the Na/K coupling ratio and total number of pumping sites.
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Bullfrog sympathetic ganglion cells treated with nicotine are hyperpolarized with application of 5-HT. This 5-HT hyperpolarization, however, was not observed if preparations were pretreated with d-TC before being treated with nicotine. When preparations were treated with ACh or carbamylcholine, which transiently depolarizes ganglion cells, hyperpolarization did take place. Such was also observed in the presence of Ringer's solution if preparations were pretreated with the K+-free Ringer's solution. These results suggested that ganglion cells were hyperpolarized by the action of 5-HT when the Na+-pump of these cells was accelerated by accumulation of intracellular Na+, as the result of a transient depolarization or extracellular K+ deficiency.
In a certain group (type 2 cells) of bullfrog sympathetic ganglion cells, an action potential exhibiting a triphasic after-potential was produced when the cells were activated by direct intracellular stimulation. This triphasic after-potential consisted of two different potential components, namely, a depolarizing response (DR) and an after-hyperpolarization. The amplitude of DR was increased by increasing the interval between stimuli. Large DRs exceeded the threshold of the cell membrane and produced repetitive firings of spike potentials. The DR was selectively depressed and eventually eliminated in a low-Ca solution. Eserine (10(-5) M) reversibly increased both the amplitude and duration of the DR, and d-tubocurarine reversibly depressed it. These results indicate that the DR of type 2 cells is the EPSP mediated by the nicotinic action of acetylcholine released from preganglionic nerve terminals. Preganglionic nerve fibers innervating type 2 cells are activated through some kind of recurrent pathway formed between them. Recurrent activation of type 2 cells seems to be thus induced when the cells are activated by direct intracellular stimulation.
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The actions of g-strophanthin, adrenaline and acetylcholine on the action potential of bullfrog ventricular muscle were studied in the Na+ -free Li+ solution, in order to examine if these actions are associated with the change of active Na+ transport. The action of g-strophanthin on the action potential, being observed in the Ringer solution, completely disappeared in the Na+-free Li+ solution. On the other hand, the actions of adrenaline and acetylcholine remained unchanged in the Na+ -free Li+ solution, except the hyperpolarizing action of adrenaline on the resting membrane. These results suggest that changes of the action potential by g-strophanthin are secondary events caused by the change of active Na+ transport, whereas those by adrenaline and acetylcholine are primary events due to the change of membrane permeability.
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1 Effects of dibutyryl cyclic adenosine 3',5'-monophosphate (dibutyryl cyclic AMP) and theophylline on bullfrog sympathetic ganglion cells were examined in order to test the hypothesis that cyclic AMP is essential for the generation of slow inhibitory postsynaptic potentials (i.p.s.ps) in these cells. 2 In the absence or presence of theophylline, dibutyryl cyclic AMP did not hyperpolarize but rather tended to depolarize ganglia that were hyperpolarized by adrenaline. 3 Theophylline augmented neither the P-potential (slow i.p.s.p.) nor adrenaline-induced hyperpolarization. 4 Thus, cyclic AMP does not seem to be essential for the generation of the slow i.p.s.p., at least in amphibian sympathetic ganglion cells.
Slow depolarizations of dorsal root nerve terminals and motoneurons, which were produced by 5-hydroxytryptamine (5-HT) applied directly to isolated bullfrog spinal cords, were recorded by the sucrose-gap method. These depolarizations were eliminated in the Ca-deficient Ringer's solution containing Mg, suggesting that these 5-HT depolarizations were not caused by a direct action of 5-HT on dorsal root nerve terminals or motoneurons but rather by actions of transmitters released from interneurons. Indeed, mephenesin, which is a selective blocker of polysynaptic transmission in the spinal cord, inhibited more markedly the 5-HT depolarization than the L-glutamate or GABA depolarization. The transmitter directly responsible for the generation of the 5-HT depolarization of dorsal root nerve terminals was not considered to be GABA as the 5-HT depolarization was not antagonized by picrotoxin. It would thus appear that 5-HT stimulates interneurons in the amphibian spinal cord and unknown transmitters released from these interneurons depolarize the dorsal root nerve terminals.
The effects of epinephrine (1 X 10(-6)--1 X 10(-5) M) on the resting membrane potential and the K+-activated hyperpolarization of bullfrog atrial heart muscles were studied by the single sucrose-gap method or by intracellular microelectrode filled with 3 M KC1. Epinephrine-induced hyperpolarization (Ep-hyperpolarization) was completely eliminated by the effect of ouabain or by removal of extracellular K+. The amplitude of K+-activated hyperpolarization, which was produced when the extracellular K+ concentration was raised from zero to 2 mM, was markedly increased in the presence of epinephrine. The membrane depolarizations, due to high extracellular K+ concentration in the presence of ouabain (5 X 10(-6) M) which completely and reversibly eliminated the K+-activated hyperpolarization, were not altered under the effect of epinephrine. These results suggested that Ep-hyperpolarization of bullfrog atrial heart muscles was due to the acceleration of electrogenic Na+ pump which produced the K+-activated hyperpolarization.
The effects of catecholamines (adrenaline, noradrenaline and isoproterenol) on ionic conductance changes during the generation of action potentials of bullfrog sympathetic and spinal ganglion cells were studied with intracellular microelectrodes. In sympathetic ganglion cells, adrenaline (3X10(-5)-1X10(-3)M) reversibly decreased the peak amplitude and positive after-potential of action potentials, and prolonged the duration of spike potentials without changes in the resting membrane potential and conductance in the Ringer solution. The maximum rates of rise and fall of spike potentials were also decreased. The action of noradrenaline was similar to that of adrenaline, but isoproterenol did not show any effects. Adrenaline (3X10(-5)-3X10(-4)M) markedly depressed the peak amplitude and maximum rate of rise of both TEA-potential and Ca-potential produced either in TEA solution containing TTX or in the isotonic CaCl2 solution. Similar actions were observed with noradrenaline but not isoproterenol. In spinal ganglion cells, catecholamines did not show any effects of the action potentials in Ringer and TEA solutions. It was concluded that adrenaline inhibited the increases in Ca2+, K+ and Na+ conductances during the generation of action potentials of sympathetic ganglion cells.