Search PubMed⌕ Search

Biomedical subjects

T Tokimasa

Publications and source records attributed to T Tokimasa.

At least 73 records · Page 4Linked to original sources
PubMed1985

Intracellular Ca2+-ions inactivate K+-current in bullfrog sympathetic neurons.

Neurons from bullfrog sympathetic ganglia were voltage clamped using a single microelectrode, in a sodium-free, calcium-rich solution containing tetraethylammonium. A brief inward calcium current was followed by a long-lasting inward current. The long-lasting inward current corresponded to a depolarizing afterpotential which followed a calcium spike under the current clamp. It was largely due to the M-channel closure. The present study indicates that massive calcium entry can cause inactivation of potassium conductance in vertebrate neurons.

Animals↗
PubMed1985

Beta-adrenergic modulation of the Na+-K+ pump in frog skeletal muscles.

Adrenaline markedly increased the ouabain-sensitive 22Na+-efflux by stimulating the Na+-K+ pump in frog skeletal muscle. The facilitatory effects of adrenaline had the following properties. The effects of adrenaline on the ouabain-sensitive Na+-efflux were observed at concentrations greater than 0.1 microM and the magnitude increased with concentration up to 10 microM. At a concentration of 30 microM, adrenaline markedly augmented the ouabain-sensitive Na+-efflux, but other biogenic amines were less effective (noradrenaline and dopamine) or ineffective (histamine and serotonin). The increase of Na+-efflux induced by 1 microM adrenaline was blocked by 3 microM propranolol, but not by 3 microM phenoxybenzamine. The properties of the facilitatory action of adrenaline on the ouabain-sensitive Na+-efflux suggest that beta-adrenoceptors have an important role in modulating the Na+-K+ pump activity in the skeletal muscle membrane. The protein complex localized in excitable membranes, namely the Na+-K+ ATPase-beta-adrenoceptor complex, may be the functional unit which operates the membrane machinery driving the Na+-K+ pump.

Animals↗
PubMed1985

Histamine is an antagonist of the acetylcholine receptor at the frog endplate.

The effects of histamine on the acetylcholine (ACh) receptor-channel complex were examined by means of voltage-clamp at the frog endplate. ACh was ionophoretically applied to the endplate. Histamine was added to the perfusate. Histamine (100 nM - 1 mM) reversibly depressed the peak amplitude of the ACh-induced inward current in a dose-dependent manner. The double reciprocal plot of the dose-response relationship between the peak ACh current and the amount of ACh applied suggested that histamine (100 microM) depressed the ACh-induced current in a competitive manner. Histamine prevented the specific ACh binding site within the receptor-channel complex from binding erabutoxin, a sea-snake venom, which binds irreversibly to the specific ACh binding site. Histamine had no detectable effects on the equilibrium potential of the endplate current but shortened the half-decay time of the endplate current in a voltage-dependent manner. It was therefore concluded that histamine blocks not only the specific ACh binding site but also interacts with the ACh-channel site. The present experiments strongly suggest that histamine can act as an antagonist to modulate nicotinic cholinergic transmission.

Acetylcholine↗
PubMed1984

Calcium entry through acetylcholine-channels can activate potassium conductance in bullfrog sympathetic neurons.

Fast B neurons in bullfrog sympathetic ganglia were voltage clamped with two microelectrodes. Acetylcholine (ACh) was applied onto the soma membrane by iontophoresis. A rapid nicotinic inward current was followed by a slow muscarinic inward current. After an addition of scopolamine to Ringer solution so as to block the muscarinic current, the nicotinic inward current was found to be followed by an outward current lasting for several hundred ms. It disappeared when the preceding nicotinic inward current was blocked by (+)-tubocurarine. The ACh-induced outward current was due to calcium entry through ACh-channels and subsequent opening of potassium channels. This may indicate that a rapid excitatory transmission leads to non-synaptic autoinhibition. The interaction between the calcium-dependent potassium conductance and the muscarinic action of ACh is proposed.

Acetylcholine↗
PubMed1984

Muscarinic agonists depress calcium-dependent gK in bullfrog sympathetic neurons.

Intracellular recordings were made from 'fast B' [9] neurons in bullfrog sympathetic ganglia. A single soma action potential was followed by a prolonged after-hyperpolarization lasting for several hundred milliseconds up to 2 s. The spike afterhyperpolarization, which is generated by calcium-dependent potassium conductance increase (gKCa) [3,20-24], was shortened by the muscarinic action of acetylcholine and oxotremorine (30-300 nM). These concentrations of muscarinic agonists were too low to cause any detectable changes in resting membrane potential, input resistance or action potential wave form. ACh released from presynaptic terminal under a physiological condition also caused the shortening of the calcium-dependent hyperpolarization. The results suggested that the shortening of calcium-dependent spike afterhyperpolarization may permit the neuron to pass the high frequency of discharge during the muscarinic excitation.

Acetylcholine↗
PubMed1984

Calcium-dependent hyperpolarizations in bullfrog sympathetic neurons.

Intracellular recordings were made from neurons in bullfrog sympathetic ganglia. Fast B and slow B neurons were identified and selected for the analysis [Dodd and Horn (1983) J. Physiol., Lond. 334, 255-269]. A single soma action potential was followed by a prolonged afterhyperpolarization lasting for several hundred ms up to 2 s. Part of the spike afterhyperpolarization was due to potassium conductance activation triggered by calcium entry during an action potential. Acetylcholine was directly applied onto the soma membrane by iontophoresis. A rapid nicotinic depolarization was followed by a slow muscarinic depolarization. The nicotinic depolarization was followed by a hyperpolarization when the muscarinic depolarization was blocked by scopolamine. This hyperpolarization was several mV in amplitude and from 1 to 10 s in duration. It disappeared when the preceding nicotinic depolarization was blocked by (+)-tubocurarine. A single fast excitatory postsynaptic potential was also followed by a hyperpolarization in the presence of scopolamine. The acetylcholine-induced hyperpolarization was due to potassium conductance activation triggered by calcium entry during the nicotinic depolarization. The present findings show that non-synaptic autoinhibition is operating in sympathetic neurons. In other words, a rapid nicotinic transmission leads to prolonged hyperpolarizations which are not mediated by any transmitters but are mediated by calcium.

Acetylcholine↗
PubMed1984

The time course of muscarinic depolarization of guinea-pig myenteric neurones.

Intracellular recordings were made from neurones in the myenteric plexus of the guinea-pig ileum in vitro. Muscarinic depolarizations were evoked by brief (1-500 ms) ionophoretic applications of acetylcholine (ACh) or other agonists. Nicotinic responses to ACh evoked by the same ionophoretic pulse had short latencies and rapid rise times, indicating close proximity of the ionophoretic pipette to the neurone membrane. The time course (duration several seconds) of the muscarinic depolarization was independent of the identity of the agonists applied (ACh, methacholine, carbachol, oxotremorine). Hyoscine and barium were ejected onto the neurones by brief (30 ms-1 s) pressure pulses applied to micropipettes. Hyoscine applied immediately after ACh, during the latency and rising phase of the muscarinic depolarization, did not antagonize the response to ACh. The same application of hyoscine immediately prior to ACh caused complete antagonism. Muscarinic depolarizations evoked by continuous application of ACh (by repeated ionophoresis or perfusion) were reversed by hyoscine. The time course of this reversal was similar to the decline of the muscarinic response following a single brief application of ACh. Barium caused a depolarization similar to that produced by muscarinic agonists in its latency, time course and temperature sensitivity, and having the same reversal potential (-90 mV). These barium potentials were not affected by hyoscine. It is suggested that neither diffusion of ACh to the receptors nor the kinetics of the agonist-receptor interaction contributes significantly to the latency and prolonged time course of the muscarinic depolarization.

Acetylcholine↗
PubMed1983

Nicotinic depolarization activates calcium dependent gK in myenteric neurons.

Intracellular recordings were made from S type neurons in the myenteric plexus of the guinea-pig ileum. Acetylcholine (ACh) was applied directly onto the soma membrane by iontophoresis with visual placement of the iontophoretic pipette. Fast nicotinic depolarizations were evoked which were followed by slow muscarinic depolarizations. After application of hyoscine to block the slow muscarinic depolarization, the nicotinic depolarization was found to be followed by a hyperpolarization. This hyperpolarization was several mV in amplitude and 1-5 s in total duration. It disappeared when the preceding nicotinic depolarization was blocked by hexamethonium. The ACh induced by hyperpolarization was due to calcium entry and subsequent opening of potassium channels.

Acetylcholine↗
PubMed1983

Depression of calcium-dependent potassium conductance of guinea-pig myenteric neurones by muscarinic agonists.

Intracellular recordings were made from myenteric neurones of the guinea-pig ileum. Muscarinic agonists acetylcholine (ACh) and oxotremorine reduced membrane potassium conductance (gK). Calcium carried into the neurone by one or more action potentials increased membrane potassium conductance (gK, Ca). The time course of the muscarinic changes in gK was compared to that of the change in gK, Ca following an action potential. The time course of conductance decrease was similar in both cases, and both time courses had the same temperature coefficient. Concentrations of ACh (100 nM) which were too low to cause a detectable reduction in resting gK shortened the duration of the gK, Ca increase which followed an action potential. Low concentrations of barium (10-100 microM) had the same effect as ACh. This was not due to a reduction in calcium entry during the action potential. Higher concentrations of ACh and barium also reduced resting membrane conductance. The conductance changes during the muscarinic action and the action potential after-hyperpolarization did not add linearly. It is proposed that muscarinic agonists and barium may act by reducing the availability of calcium ions at a site within the membrane which controls gK.

Acetylcholine↗
PubMed1982

Effects of histamine on acetylcholine release in bullfrog sympathetic ganglia.

The effects of histamine on the release of acetylcholine (ACh) from bullfrog sympathetic preganglionic nerve terminals were examined by means of intracellular microelectrode techniques. Low concentrations of histamine (1, 3 muM) increased the amplitude of fast excitatory postsynaptic potentials (fast EPSPs) and ACh quantal content, while high concentrations (100, 300 muM) decreased the amplitude and content. Amplitudes of miniature EPSPs and ACh potentials were not affected by histamine (0.3-300 muM). The facilitatory effect of histamine on fast EPSPs disappeared in the presence of mepyramine, whereas the depressant effect of histamine on fast EPSPs disappeared in the presence of cimetidine. These results suggest that histamine has facilitatory and depressant actions on ACh release. The facilitatory action is probably mediated by the H1-receptor and the depressant action by the H2-receptor, both of which are located at the presynaptic nerve terminals of bullfrog sympathetic ganglia.

Acetylcholine↗
PubMed1982

The calcium-activated potassium conductance in guinea-pig myenteric neurones.

1. Intracellular recordings were made from guinea-pig myenteric neurones in vitro.2. From one to sixty action potentials were followed by an afterhyperpolarization, the amplitude and duration of which increased with the number of preceding action potentials.3. The afterhyperpolarization reversed its polarity at a membrane potential of -91 mV. This value changed by 58 mV when the potassium concentration of the perfusing solution was changed ten-fold.4. The afterhyperpolarization was abolished in calcium-free solutions. It was shortened in low calcium (1.2 mM) solutions and prolonged in solutions which contained high (5.0 mM) calcium concentrations, TEA (1 mM) or caffeine (1 muM).5. The conductance increase during the afterhyperpolarization (g(K, Ca)) was calculated from the amplitude of electrotonic potentials, taking advantage of the lack of membrane rectification in the range -60 to -90 mV. Peak g(K, Ca) increased as the number of action potentials was increased, but was relatively independent of membrane potential in this range.6. g(K, Ca) declined with a time course which was single exponential (time constant 1.5-5 s) following one to six action potentials, and double exponential (time constants about 3 and 12 s) following fifteen to sixty action potentials.7. It is concluded that the calcium which enters the neurone during the action potential elevates the membrane potassium conductance. The time course of this conductance increase probably reflects the free intracellular calcium concentration, and therefore describes the calcium sequestration or extrusion process.

Action Potentials↗
PubMed1982

Muscarinic agonists inactivate potassium conductance of guinea-pig myenteric neurones.

1. The effects of muscarinic agonists applied both by perfusion and ionophoresis to myenteric neurones of the guinea-pig ileum were investigated by intracellular recording methods. 2. Perfusion with muscarinic agonists (acetylcholine, oxotremorine, methacholine, bethanechol) in concentrations of 100 nM to 10 microM caused membrane depolarizations. Brief ionophoretic applications of oxotremorine, or acetylcholine in the presence of hexamethonium, evoked depolarizations with a latency of 100 ms to 1 s and a duration of 5-60 s. 3. The depolarizations were completely antagonized by low concentrations (1-10 nM) of the muscarinic antagonists hyoscine or atropine. 4. The latency and time course of the muscarinic depolarizations were about one thousand times longer than those of nicotinic responses evoked in the same cell by acetylcholine applied from the same ionophoresis electrode. 5. The muscarinic depolarization was associated with a conductance decrease and reversed polarity at a membrane potential close to the potassium equilibrium potential. 6. The muscarinic depolarization became smaller but did not disappear completely during prolonged (up to 60 min) perfusion or repeated (more than 0.02 Hz) ionophoretic applications of muscarinic agonists. 7. Lower concentrations (3-30 nM) of oxotremorine, which did not change membrane potential, reduced the amplitude and duration of the calcium-dependent increase in potassium conductance which follows a burst of action potentials. 8. It is concluded that the muscarinic depolarization of myenteric neurones is due to potassium inactivation.

Action Potentials↗
PubMed1982

Muscarinic presynaptic inhibition of synaptic transmission in myenteric plexus of guinea-pig ileum.

1. The effect of oxotremorine (300 pM to 30 nM) on synaptic transmission in isolated myenteric ganglia of guinea-pig ileum was investigated with intracellular recording techniques. 2. These low concentrations of oxotremorine had no effect on the resting membrane potentials or on the membrane conductance. 3. Oxotremorine reduced the amplitude of the fast excitatory post-synaptic potential (e.p.s.p.) but did not reduce the amplitude of nicotinic responses to ionophoretic application of acetylcholine (ACh). This effect of oxotremorine on the fast e.p.s.p. was dose-dependent; the amplitude was reduced by about 45% by 30 nM-oxotremorine. 4. Non-cholinergic slow e.p.s.p.s evoked by repetitive presynaptic nerve stimulation were reduced in amplitude by oxotremorine. 5. Hyoscine or atropine (1 nM) completely antagonized both these effects of oxotremorine (30 nM). 6. Muscarinic antagonists alone increased the amplitude of second and subsequent fast e.p.s.p.s when these were evoked at intervals of 1 s, and increased the amplitude and duration of the slow e.p.s.p. evoked by repetitive presynaptic nerve stimulation. 7. The results indicate that muscarinic receptor activation inhibits the release of the transmitters which mediate both the fast and the slow e.p.s.p.s and that this can occur with physiologically released ACh during repetitive presynaptic nerve activity.

Acetylcholine↗
PubMed1982

Muscarinic synaptic potentials in guinea-pig myenteric plexus neurones.

1. Intracellular recordings were made from neurones in the myenteric plexus of the guinea-pig ileum in vitro. 2. A single pulse stimulus to the presynaptic fibres entering a myenteric ganglion elicited a fast excitatory post-synaptic potential (e.p.s.p.) in type 1 (S) cells: in about one-quarter of cells this was followed by a slow e.p.s.p. 3. The slow e.p.s.p. had a latency of 122 ms and a total duration of 3-15 s. It was reversibly abolished by hyoscine (1 microM). 4. Both the fast e.p.s.p. and the slow e.p.s.p. could be mimicked by ionophoretic application of a single brief pulse of acetylcholine (ACh) to the neurone soma. The depolarization which mimicked the fast e.p.s.p. was reversibly blocked by hexamethonium. The depolarization which mimicked the slow e.p.s.p. was reversibly blocked by hyoscine. 5. Type 2 (AH) neurones did not show fast or slow e.p.s.p.s in response to a single pulse stimulus. Stimuli comprising many pulses (typically 10 Hz for 3 s) evoked a slow e.p.s.p. in which the initial portion was partly blocked by hyoscine, but which was predominantly non-cholinergic.

Acetylcholine↗
PubMed1982

Desensitization of the muscarinic receptor controlling action potential of bullfrog atrial muscles.

Action potentials of the bullfrog atrial muscle, being depressed by carbachol in concentrations of (1-5) X 10(-7) M, were found to show a slow recovery when application of the drug was sustained. The rate of onset of recovery largely varied depending on individual preparations. The recovery of action potentials was neither due to changes in the ionic distribution across the membrane nor to a secondary action of catecholamine which was released by the nicotinic action of carbachol on sympathetic nerve terminals. These results suggested that the muscarinic ACh receptor responsible for the depression of action potentials showed desensitization to the action of its agonist. The slow inward current recorded by the voltage-clamp experiment showed a decrease and subsequent slow recovery in the presence of carbachol. This suggested that the muscarinic ACh receptor associating with the ionic channel of the slow inward current showed desensitization. It may be suggested on the basis of these experimental results that 1) the muscarinic ACh receptor of bullfrog atrial muscle may compose a receptor-ionic channel complex (RICC) with voltage-dependent CA2+ channel and 2) the molecular reaction between this RICC and agonist may be comparable to that occurring in the nicotinic RICC of the frog end-plate.

Acetylcholine↗