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Biomedical subjects

M Sugimori

Publications and source records attributed to M Sugimori.

At least 91 records · Page 5Linked to original sources
PubMed1985

Ionic currents and firing patterns of mammalian vagal motoneurons in vitro.

The electrophysiological properties of guinea-pig dorsal vagal motoneurons were studied in an in vitro slice preparation. Antidromic, orthodromic and direct stimulation of the neurons demonstrated that the action potential is comprised of several distinct components: a fast initial spike followed by afterdepolarization and an early and a late afterhyperpolarizations. The fast initial spike and the early afterhyperpolarization were blocked by tetrodotoxin and tetraethylammonium ions, respectively. The afterdepolarization (present on the falling phase of the spike) and the late afterhyperpolarization were blocked by the addition of ions known to block calcium conductance (CdCl2, CoCl2 or MnCl2), indicating close association between these two potentials. Prolonged outward current injection through the recording electrode produced two different firing patterns, depending on the initial level of the membrane potential. From resting potential (usually -60 mV) the firing pattern was characterized by a short train of action potentials appearing shortly after the onset of the depolarization step. By contrast, when the depolarization was delivered from a hyperpolarized membrane potential level, a short train of repetitive firing appeared after an initial delay of 300-400 ms. The membrane current responsible for this initial reduction in excitability was studied by means of a single-electrode voltage-clamp technique. The magnitude, direction and kinetics of such current flow are consistent with the presence of early potassium current (IA), partly inactive at the resting potential. Synaptic activation of vagal motoneurons could be obtained by electrical stimulation of the tissue surrounding the vagal nucleus or by direct activation of the vagal nerve. Perivagal stimulation generated excitatory and inhibitory synaptic potentials which could be reversed by shifting the membrane potential. Vagal nerve stimulation, in addition to the antidromic activation of the cells, generated depolarizing responses which were unitary in nature and did not show much sensitivity to shifts in membrane potential. Perivagal and vagal nerve-evoked depolarizations could generate action potentials as well as partial dendritic spikes. We conclude that spike electroresponsiveness in vagal motoneurons is generated by voltage-dependent Na+ and Ca2+ conductances. In addition, the Ca2+-dependent current triggers a K+ conductance which is responsible for modulating the firing frequency obtained from the normal resting level.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1985

Direct action of mazindol on guinea-pig ventromedial hypothalamic neurons: intracellular studies in slice preparation.

Neuronal responses in the ventromedial hypothalamic nucleus (VMH) to mazindol (MZD) were examined by intracellular recordings in hypothalamic slices in vitro. Bath application of MZD caused depolarization of the membrane by 8.0 +/- 3.4 mV (mean +/- S.D.) associated with an increase in the input membrane resistance (23.0 +/- 5.8%) among 20% of the cells examined. Current-voltage plots, obtained simultaneously, showed the reversal potential between -80 and -90 mV. These results indicate that MZD depolarizes VMH neurons by reducing the K+ conductance, through a mechanism similar to that of glucose, and the anorectic action of MZD can be explained by its direct effects on the VMH.

Animals↗
PubMed1985

Immunological study of the rat hypothalamic ventromedial nucleus.

Specific anti-sera were prepared by injecting the homogenates of rat ventromedial nucleus (VMH) and caudate nucleus (Cd) into the rabbit. Anti-VMH serum, after absorption of common components in rat normal serum and anti-Cd serum, reacted specifically to the rat VMH with only one precipitation line. Anti-VMH serum was successfully applied to 80 VMH neurons by electrophoresis through 5 barreled micropipettes. Fresh anti-VMH serum caused an irreversible response (increase and subsequent sudden cessation of firing) in 8 of the 25 VMH neurons tested. Anti-VMH serum reversibly inhibited 32 of 80 VMH neurons and 13 of these were also tested with glucose. Discharge rates of 12 of the 13 neurons increased by glucose. Most of these neurons were not affected by anti-Cd serum or normal rabbit serum. Results of these immunological and electrophysiological studies suggest the existence of specific membrane receptor binding sites on the glucoreceptor neurons in the VMH. These sites afford one route for producing the excitatory effect that glucose has on VMH neurons.

Animals↗
PubMed1985

Intraterminal injection of synapsin I or calcium/calmodulin-dependent protein kinase II alters neurotransmitter release at the squid giant synapse.

Synapsin I and calcium/calmodulin-dependent protein kinase II were pressure-injected into the preterminal digit of the squid giant synapse to test directly the possible regulation of neurotransmitter release by these substances. Neurotransmitter release was determined by measuring the amplitude, rate of rise, and latency of the postsynaptic potential generated in response to presynaptic depolarizing steps under voltage clamp conditions. Injection of dephosphosynapsin I decreased the amplitude and rate of rise of the postsynaptic potential, whereas injection of either phosphosynapsin I or heat-treated dephosphosynapsin I was without effect. Conversely, injection of calcium/calmodulin-dependent protein kinase II, which phosphorylates synapsin I on site II, increased the rate of rise and amplitude and decreased the latency of the postsynaptic potential. The effects of these proteins were observed without any detectable change in the initial phase of the presynaptic calcium current. A synapsin I-like protein and calcium/calmodulin-dependent protein kinase II were demonstrated by biochemical and immunochemical techniques to be present in squid nervous tissue. The data support the hypothesis that synapsin I regulates the availability of synaptic vesicles for release; we propose that calcium entry into the nerve terminal activates calcium/calmodulin-dependent protein kinase II, which phosphorylates synapsin I on site II, dissociating it from the vesicles and thereby removing a constraint in the release process.

Animals↗
PubMed1982

Transmission by presynaptic spike-like depolarization in the squid giant synapse.

Synaptic transmission produced by artificially generated presynaptic depolarizations, having the same waveform as normal presynaptic action potentials, was studied in the squid giant synapse. These stimulated spikes produced synaptic transmission virtually indistinguishable from that obtained with the original presynaptic spike activation. The technique allows a direct determination of the onset and amplitude of the Ca current, ICa, triggered by the presynaptic action potential and the relationship between ICa and postsynaptic response. The results closely resemble theoretical predictions by a previously published model for synaptic transmission in this synapse and demonstrate that ICa occurs at the falling phase of the presynaptic spike.

Action Potentials↗
PubMed1982

Effect of Nocardia rubra cell-wall skeleton on colony-stimulating activity and myeloid colony formation.

The in vivo effect of Nocardia rubra cell-wall skeleton (N-CWS) was studies on the generation of bone marrow granulocyte-macrophage progenitor cells [colony-forming units culture (CFU-c)] and on the levels of myeloid colony-stimulating activity (CSA) in the conditioned medium of the lung (LCM) and serum obtained from mice. In vitro bone marrow culture showed that intraperitoneal (ip) treatment of mice with N-CWS markedly enhanced CFU-c formation induced by stimuli in LCM or serum derived from lipopolysaccharide (LPS)-treated mice. The LCM and serum of mice injected with N-CWS ip were also prepared and assayed for CSA. CSA levels with N-CWS-LCM as well as LPS-LCM used as the standard CSA were markedly greater than those achieved with control LCM. N-CWS-serum also showed a low but significant level of CSA. The CSA level of N-CWS-LCM was maximal at 3 to 5 days after N-CWS injection. These results raise the possibility that enhanced CSA production might be a major mechanism for N-CWS stimulation of granulocyte-macrophage production.

Animals↗
PubMed1981

Isolated mammalian brain in vitro: new technique for analysis of electrical activity of neuronal circuit function.

A new technique is described that allows neurobiological research in mammalian brain in vitro. The approach utilizes the vascular system to irrigate portions of the brain-in this case the brain stem and cerebellum "en block." The preparation, which can survive for about 10 hours, demonstrates normal field potentials following stimulation of either the surface or the underlying white matter at both cerebellar and brain stem levels. Intracellular studies at both these levels indicate cellular activity in every way similar to the in vivo or the slice preparation from the same regions. This new technique offers potential for the study of ionic mechanisms underlying electrical activity as well as neurochemistry, neuroanatomy, neuropharmacology, and neuroendocrinology.

Action Potentials↗
PubMed1980

Electrophysiological properties of in vitro Purkinje cell somata in mammalian cerebellar slices.

1. The electrical activity of Purkinje cells was studied in guinea-pig cerebellar slices in vitro. Intracellular recordings from Purkinje cell somata were obtained under direct vision, and antidromic, synaptic and direct electroresponsiveness was demonstrated. Synaptic potentials produced by the activation of the climbing fibre afferent could be reversed by direct membrane depolarization. 2. Input resistance of impaled neurones ranged from 10 to 19 M omega and demonstrated non-linearities in both hyperpolarizing and depolarizing directions. 3. Direct activation of a Purkinje cell indicated that repetitive firing of fast somatic spikes (s.s.) occurs, after a threshold, with a minimum spike frequency of about 30 spikes/sec, resembling the '2-class' response of crab nerve (Hodgkin, 1948). 4. As the amplitude of the stimulus was increased, a second form of electroresponsiveness characterized by depolarizing spike bursts (d.s.b.) was observed and was often accomppanied by momentary inactivation of the s.s. potentials. Upon application of tetrodotoxin (TTX) or removal of Na+ ions from the superfusion fluid, the s.s. potentials were abolished while the burst responses remained intact. However, Ca conductance blockers such as Co, Cd, Mn and D600, or the replacement of Ca by Mg, completely abolish d.s.b.s. 5. If Ca conductance was blocked, or Ca removed from the superfusion fluid without blockage of Na conductance, two types of Na-dependent electroresponsiveness were seen: (a) the s.s. potentials and (b) slow rising all-or-none responses which reached plateau at approximately -15 mV and could last for several seconds. These all-or-none Na-dependent plateau depolarizations outlasted the stimulus and were accompanied by a large increase in membrane conductance. Within certain limits the rate of rise and amplitude of the plateau were independent of stimulus strength. The latency, however, was shortened as stimulus amplitude was increased. These potentials were blocked by TTX or by Na-free solutions. 6. Substitution of extracellular Ca by Ba or intracellular injection of tetraethylammonium generated prolonged action potentials lasting for several seconds and showing a plateau more ositive than those obtained in norrmal circumstances by either non-inactivating Na or Ca currents. 7. Spontaneous firing of the Purkinje cell was characterized by burst-like activity consisting of both s.s. and d.s.b. responses. Addition of TTX to the bath left the basic spontaneous activity and its frequency unaltered, indicating tha Ca spiking and Ca-dependent K conductance changes are the main events underlying this oscillatory behaviour. 8...

Action Potentials↗
PubMed1980

Electrophysiological properties of in vitro Purkinje cell dendrites in mammalian cerebellar slices.

1. Intradendritic recordings from Purkinje cells in vitro indicate that white matter stimulation produces large synaptic responses by the activation of the climbing fibre afferent, but antidromic potentials do not actively invade the dendritic tree. 2. Climbing fibre responses may be reversed in a manner similar to that observed at the somatic level. However, the reversal does not show the biphasicity often seen at somatic level. 3. Input resistance of these dendrites was found to range from 15 to 30 M omega. The non-linear properties seen at the somatic level for depolarizing currents are also encountered here. However, there seems to be less anomalous rectification. 4. Detailed analysis of repetitive firing of Purkinje cells elicited by outward DC current shows that, as in the case of the antidromic invasion, the fast somatic potentials (s.s.) do not invade the dendrite actively. However, the dendritic spike bursts (d.s.b.s) interposed between the s.s. potentials are most prominent at dendritic level. 5. Two types of voltage-dependent Ca responses were observed. At low stimulus level a plateau-like depolarization is accompanied by a prominent conductance change; further depolarization produces large dendritic action potentials. These two classes of response are TTX-resistant but are blocked by Cd, Co, Mn or D600, or by the removal of extracellular Ca. 6. Following blockage of the Ca conductance, plateau potentials produced by a non-inactivating Na conductance are observed mainly near the soma indicating that this voltage-dependent conductance is probably associated with the somatic membrane. 7. Spontaneous firing in Purkinje cell dendrites is very similar to that observed at the soma. However, the amplitude of these bursts is larger at dendritic level. It is further concluded that these TTX-insensitive spikes are generated at multiple sites along the dendritic tree. 8. Six ionic conductances seem to be involved in Purkinje cell electroresponsiveness: (a) an inactivating and (b) a non-inactivating Na conductance at or near the soma, (c) a spike- and (d) a plateau-generating Ca conductance, and (e) voltage-dependent and (f) Ca-dependent K currents. 9. The possible role of these conductances in Purkinje cell integration is discussed.

Action Potentials↗
PubMed1978

Response properties and electrical constants of caudate nucleus neurons in the cat.

1. Response properties and passive electrical constants were assessed for caudate nucleus neurons in pentobarbital-anesthetized cats. The neurons studied were those which could be monosynaptically excited by substantia nigra and thalamic (centromedian-parafascicular) stimulation. 2. Input resistance and membrane time constant were estimated from the plateau value and time course, respectively, of the neuronal membrane response to intracellularly applied current pulses. The average values obtained were 16.5 Momega and 11.3 ms. Specific resistance and capacitance values were calculated. 3. Single or repetitive spikes were readily evoked by nigral or thalamic stimuli or by the application of direct depolarizing currents. Spike thresholds were higher for direct than for synaptic activation (7.2 vs. 5.6 mV). 4. Direct depolarizing stimuli with durations up to 600 ms elicited repetitive discharge with little adaptation of firing rate. The maximum discharge rates induced by direct stimuli were near 200 spikes per second. 5. The intracellular application of tetraethylammonium chloride (TEA) produced spike-prolongation effects in caudate neurons that were similar to the effects reported for other nerve membrane. 6. The probable identity of the recorded neurons as medium spiny neurons was discussed and, in addition, it was proposed that the characteristic silence of these cells is not likely due to intrinsic membrane specialization.

Action Potentials↗