Search PubMed⌕ Search

Biomedical subjects

K Kuba

Publications and source records attributed to K Kuba.

At least 73 records · Page 4Linked to original sources
PubMed1987

Regulation of two ion channels by a common muscarinic receptor-transduction system in a vertebrate neuron.

In bullfrog sympathetic ganglion cells, muscarine produced an inward current (Imus) through the activation of a subtype (M1) of muscarinic acetylcholine receptor (mAChR) by suppressing an outward M-current (IM), and/or activating cation-selective current (ID; see below). The former was induced with a potency (Kd = 0.5 microM) higher than the latter (Kd = 5 microM) before and after blocking a fraction of the receptor with an irreversible blocker. Activators of protein kinase C mimicked muscarine's actions. Blocking IM by Ba2+ increased ID. These results suggest that activation of M1-mAChR both closes M-channel and opens cation-selective D-channel through phosphoinositide breakdown and the subsequent activation of protein kinase C and that a difference in potency at the last step of the cascade determines the order in which channels are regulated.

Animals↗
PubMed1987

The Ca2+-sensitive K+-currents underlying the slow afterhyperpolarization of bullfrog sympathetic neurones.

Ca2+-sensitive K+ currents involved in the slow afterhyperpolarization (a.h.p.) of an action potential of bullfrog sympathetic neurones were studied with a single-electrode voltage clamp method. The outward tail current (IAH) generated after the end of a depolarizing command pulse (from the holding potential of -60 mV to 0 mV, 5-20 ms in duration), mimicking an action potential, was separated into at least two exponential components (IAHf and IAHs). They were identified as K+ currents, since their reversal potentials were close to the K+ equilibrium potential and they were sensitive to external K+. The time constant of IAHf (tf; 44 ms at -60 mV) was decreased by membrane hyperpolarization from -40 to -80 mV, while that of IAHs (ts; 213 ms) remained constant. Removal of external Ca2+ or addition of Cd2+ significantly decreased the IAHs amplitude (As) and tf without a change in ts and the IAHf amplitude (Af). On the other hand, increasing Ca2+ influx by applying repetitive command pulses enhanced both Af and As with negligible effects on tf and ts, and produced a much slower component. Intracellular injection of EGTA reduced Af with no effect on tf, and increased As with a decreased ts. Both muscarine and (+/-)-tubocurarine, which reduced IAHs, hardly affected IAHf. These results indicate that a.h.p. is induced by the activation of two distinct Ca2+-dependent K+ channels, which differ in voltage sensitivity, Ca2+-dependence and pharmacology.

Action Potentials↗
PubMed1987

Mechanisms regulating the adrenaline-induced long-term potentiation in bullfrog sympathetic ganglia.

Two regulatory mechanisms on the long-term potentiation of transmitter release induced by adrenaline (adr.-l.t.p.) in bullfrog sympathetic ganglia were studied by recording intracellularly the fast excitatory postsynaptic potentials. An increase in exposure time to adrenaline from 10 min to 60 min did not enhance the magnitude of adr.-l.t.p. However, increasing an exposure time to dibutyryl cyclic AMP (1 mM) up to 60 min progressively enhanced the magnitude of the nucleotide-induced potentiation, indicating the desensitization of the beta-adrenoceptor. The desensitization remained at 20 min after the removal of adrenaline in all the five cells but disappeared at 60-90 min in four cells out of eight. Under the latter condition, the second l.t.p. was summated on the first one. Dibutyryl cyclic GMP (100 microM) blocked the generation of the l.t.p. induced by dibutyryl cyclic AMP (1 mM) as well as that of adr.-l.t.p. Muscarine (10 microM) or adenosine (1 mM), a possible candidate for raising intraterminal cyclic GMP, did not significantly affect adr.-l.t.p. These results suggest that adr.-l.t.p. is regulated by the desensitization of beta-adrenoceptor and a process which involves endogenous cyclic GMP acting on a step subsequent to the cyclic AMP production.

Adenosine↗
PubMed1987

Role of ion conductance changes and of the sodium-pump in adrenaline-induced hyperpolarization of rat diaphragm muscle fibres.

The ionic mechanism of membrane hyperpolarization induced by adrenaline in rat diaphragm muscle fibres was studied. Removal of the extracellular K+ ([K+]o) from Krebs-Ringer solution initially increased the resting membrane potential and then caused an increase in the intracellular Na+ activity ([Na+]i) and a decrease in the intracellular K+ activity ([K+]i). All the changes were maintained for more than 3 h. Application of ouabain (0.1 mM) or lowering the temperature rapidly reduced the resting potential by about 10 mV in the K+-free solution. It then produced further progressive decreases in resting potential and in [K+]i and a progressive increase in [Na+]i. These observations indicate that an electrogenic Na-pump operates in the K+-free solution. Removal of most of the Cl- in the K+-free solution did not affect the resting potential or the magnitude of the initial decrease produced by ouabain, despite an increased input resistance; this result implies a passive distribution of Cl-. Adrenaline (30-60 microM) either added to the bathing solution or applied to the membrane by ionophoresis produced a hyperpolarization (3-10 mV: adrenaline hyperpolarization), the amplitude of which was decreased with a rise in [K+]o and increased with a reduction in [K+]o, but unaffected by the removal of Cl-. Adrenaline produced an increase in input resistance, the relative magnitude (17-18%) of which was constant whether external K+ or Cl- was removed. In contrast, a conditioning membrane hyperpolarization hardly affected the resistance. Ouabain (0.1 mM) or low temperature (8-10 degrees C) abolished both the hyperpolarization and the increased input resistance induced by adrenaline. The [K+]i, [Na+]i and the peak of the action potential remained unchanged after a 20 min exposure to adrenaline (30 microM). The hyperpolarization induced by the replacement of all Na+ with Tris (Tris-hyperpolarization) in the K+-free solution was depressed by 39% during the early period (4-31 min) of exposure to adrenaline (30 microM), while it was enhanced by 26% during the later period (80-130 min). The initial depression suggested a decrease in the ratio of the membrane permeability for Na+ (PNa) to that for K+ (PK). These results suggest that the adrenaline hyperpolarization is generated largely by a decrease in PNa/PK, which is associated with the activity of the Na-pump.

Animals↗
PubMed1986

Differential effects of apamin on Ca2+-dependent K+ currents in bullfrog sympathetic ganglion cells.

In B-type neurones of bullfrog sympathetic ganglia, apamin (10 nM) suppressed the Ca2+-dependent K+ current (IAH) involved in the afterhyperpolarization of an action potential, while it did not affect the Ca2+-dependent K+ current (Ic) underlying the spike repolarization. IAH was further separated into two exponential components which were differentially affected by apamin, voltage and alterations in Ca2+ influx, suggesting the existence of 3 different types of Ca2+-dependent K+ channel in bullfrog sympathetic neurones.

Action Potentials↗
PubMed1986

Mechanism of long-term potentiation of transmitter release induced by adrenaline in bullfrog sympathetic ganglia.

A mechanism of the long-term potentiation of transmitter release induced by adrenaline (ALTP) was studied by recording intracellularly the fast excitatory postsynaptic potentials (fast EPSPs). The ALTP was produced during the blockade of K+ channels at the presynaptic terminals by tetraethylammonium (TEA). The synaptic delay, possibly reflecting a relative change in the duration of an action potential at the presynaptic terminal, was not changed during the course of the ALTP. By contrast, it was significantly lengthened by TEA and other K+ channel inhibitors (4-aminopyridine and Cs+) that markedly enhanced the evoked release of transmitter. The magnitude of facilitation of the fast EPSP, induced by a conditional stimulus to the preganglionic nerve, was decreased during the generation of the ALTP, but was unchanged during the potentiation of transmitter release caused by TEA. These results, together with theoretical considerations applying the residual Ca2+ hypothesis to the facilitation, suggest that the enhancement of transmitter release during the ALTP is not caused by an increased Ca2+ influx during a presynaptic impulse owing to the blockade of K+ channel or the modulation of Ca2+ channel, but presumably is induced by a rise in the basal level of free Ca2+ in the presynaptic terminal.

Animals↗
PubMed1986

Long-term potentiation of transmitter release induced by adrenaline in bull-frog sympathetic ganglia.

Long-term potentiation (l.t.p.) of transmitter release induced by adrenaline in bull-frog sympathetic ganglia was studied using intracellular recording techniques. The quantal content of the fast excitatory post-synaptic potentials (fast e.p.s.p.s: evoked by the nicotinic action of acetylcholine) was potentiated for more than several hours after treatment with adrenaline (1-100 microM). A similar l.t.p. of quantal content was produced consistently by isoprenaline (10 microM) and only in a certain fraction of cells by dopamine (10 microM). The l.t.p. induced by adrenaline (10 microM) was blocked by a beta-antagonist, propranolol (1 microM), but not by an alpha-antagonist, phenoxybenzamine (1 microM). Dibutyryl adenosine 3',5'-phosphate (dibutyryl cyclic AMP) (0.8-1.0 mM), adenosine 3',5'-phosphate (cyclic AMP) (4 mM), 3-isobutyl-1-methylxanthine (10 microM), caffeine (1-2 mM), and cholera toxin (2 micrograms ml-1) applied for 20-30 min, all caused the l.t.p. of quantal content. By contrast, adenosine 5'-phosphate (AMP) (4 mM) and adenosine (4 mM) had no potentiating action. Treatment of the ganglion with adrenaline (2.5-160 microM) or dibutyryl cyclic AMP (4 mM) for 15-30 min resulted in the l.t.p. of the frequency of miniature e.p.s.p.s. The l.t.p. of quantal content induced by adrenaline was markedly suppressed by lowering temperature from 20-25 degrees C to 11-13 degrees C, and blocked by dibutyryl guanosine 3',5'-phosphate (dibutyryl cyclic GMP) (100 microM) consistently when applied together, but inconsistently when given after adrenaline. The post-synaptic sensitivity to acetylcholine was unchanged for at least 1 h after exposure to adrenaline (2.5-160 microM) or dibutyryl cyclic AMP (0.8-4 mM). It can be concluded that adrenaline produces l.t.p. of transmitter release by activating a cyclic-AMP-dependent metabolic process through the activation of beta-adrenoceptors, and that this mechanism is presumably regulated by a process involving endogenous guanosine 3',5'-phosphate (cyclic GMP).

1-Methyl-3-isobutylxanthine↗
PubMed1985

The effects of exercise and weight loss on plasma lipids in young obese men.

We studied the independent and combined effects of exercise training and weight loss on blood lipids under fixed diet and exercise conditions. Twenty-one obese sedentary men were randomly allocated to one of four treatment groups: (1) inactive and constant weight (control), (2) exercise training and constant weight, (3) inactive and weight loss, and (4) exercise training and weight loss. There were three study periods: a 3 week baseline period inactive and on an isocaloric diet, a 12 week treatment period, and a 3 week weight stabilization period. Exercise consisted of treadmill walking at an energy cost of 3500 kcal/wk for groups 2 and 4 with replacement caloric intake only in group 2. Group 3 reduced caloric intake by 3500 kcal/wk during the treatment period. Weight loss for groups 3 and 4 were 13.4 pounds and 13.7 pounds, respectively. Maximal oxygen uptake (mL/min) increased 6% in both exercise groups (2 and 4), and percent body fat decreased only in these groups. Regression analysis by group assignment on HDL cholesterol (HDL-C) showed that the inactivity-weight loss modality (group 3) and the exercise-constant weight modality (group 2) each significantly increased HDL-C, with an additive effect of exercise and weight loss (group 4). The rate of HDL-C change differed significantly between groups (P = 0.01). HDL-C increased 0.63, 0.61, and 1.89 mg/dL per 3 weeks or 2%, 2.4%, and 5.5% above baseline levels in groups 2, 3, and 4, respectively, while the control group decreased 0.11 mg/dL. Plasma triglycerides and very low-density lipoprotein (VLDL) cholesterol increased with exercise at constant weight (group 2) and decreased with exercise associated with weight loss (group 4). In conclusion, exercise and weight loss separately and independently increase HDL-C, and their effects are additive.

Adult↗
PubMed1985

The mechanism of the inhibitory action of adrenaline on transmitter release in bullfrog sympathetic ganglia: independence of cyclic AMP and calcium ions.

The effects of adrenaline and dibutyryl adenosine 3':5' - cyclic monophosphate (db cyclic AMP) on nicotinic transmission in bullfrog sympathetic ganglia were compared by use of an intracellular recording technique. The evoked release of transmitter, acetylcholine (ACh), was decreased in the presence of adrenaline (10-100 microM), while the postsynaptic sensitivity to ACh was unchanged (10 microM adrenaline) or slightly reduced (100 microM). Transmitter release was similarly inhibited by dopamine (10 microM), but not by isoprenaline (10 microM). The inhibitory action of adrenaline on transmitter release was blocked by phenoxybenzamine but not by propranolol. The inhibition of transmitter release was independent of the external calcium concentration. The evoked release of transmitter and the electrical properties of the postsynaptic membrane were unchanged during exposure to db cyclic AMP (1-4 mM), while the postsynaptic sensitivity to ACh was slightly but significantly depressed. The spontaneous release of transmitter in a high K+ (10 mM) solution was decreased in the presence of adrenaline (100-300 microM), but unchanged with db cyclic AMP (4 mM). In contrast to the effects during exposure, both the evoked and spontaneous release of transmitter were enhanced after the removal of adrenaline or db cyclic AMP. Neither adrenaline (100 microM) nor db cyclic AMP (4 mM) affected the presynaptic spike and synaptic delay. It is concluded that adrenaline mainly inhibits the release of ACh from the presynaptic terminals through its alpha-action, while db cyclic AMP reduces slightly the postsynaptic sensitivity to ACh and that both agents facilitate transmitter release when they are removed from the presynaptic terminals. It is further suggested that the inhibitory action of adrenaline is independent of endogenous cyclic AMP and calcium ions.

Acetylcholine↗
PubMed1985

Long-term potentiation of transmitter release induced by repetitive presynaptic activities in bull-frog sympathetic ganglia.

Long-lasting potentiation of transmitter release induced by repetitive presynaptic activities in bull-frog sympathetic ganglia was studied by recording intracellularly fast excitatory post-synaptic potentials (fast e.p.s.p.s.). Following a brief period of post-tetanic potentiation or depression (less than 10 min), the amplitude of the fast e.p.s.p. was potentiated for a period between several tens of minutes and more than 2 h in response to tetanic stimulation of the preganglionic nerve in twenty-one out of twenty-eight cells. Quantal analysis revealed that this long-term potentiation of the fast e.p.s.p. (l.t.p.) was accompanied by an increase in quantal content m (in nine out of twenty-one cells), quantal size (four cells) or both (eight cells). The increased quantal content (presynaptic l.t.p.) declined exponentially (ten cells) or decayed gradually to a certain enhanced level which lasted several hours. In contrast, the increased quantal size grew with a relatively long latency (10-25 min) and remained relatively constant for at least 2 h. The magnitude of presynaptic l.t.p. increased with increased duration of the presynaptic tetanus (33 Hz) from 2 to 5 s. No l.t.p. was elicited by a 1-s tetanus, whereas the time course appears to be independent of the tetanus duration and the magnitude of l.t.p. There was a positive correlation between the magnitude of presynaptic l.t.p. and the pre-tetanic quantal content up to m = 3, but the former deviated from linear regression when the value of the latter exceeded 3. No l.t.p. occurred when quantal content was less than 0.5. A tetanus (33 Hz, 10 s) applied in Ca2+-free solution elicited no presynaptic l.t.p., while the same tetanus in normal Ringer solution produced a large presynaptic l.t.p. Presynaptic l.t.p. was enhanced in magnitude at low temperature (8-10 degrees C). These results demonstrate the existence of a use-dependent, long-term potentiation of transmitter release in bull-frog sympathetic ganglia. Several possible mechanisms are discussed in terms of Ca2+-buffering mechanisms of the presynaptic nerve terminals.

Action Potentials↗
PubMed1985

Effects of K+-channel blockers on transmitter release in bullfrog sympathetic ganglia.

Effects of K+-channel blockers, tetraethylammonium (TEA), 4-aminopyridine (4-AP) and Cs+ on synaptic transmission were studied with an intracellular electrode in bullfrog sympathetic ganglia. TEA (25-500 microM), 4-AP (0.6-5 microM) and Cs+ (50 microM-10 mM) all increased the quantal content of the fast excitatory postsynaptic potential in a dose-dependent manner. The effects of TEA were rapid in onset and recovery, whereas those of 4-AP and Cs+ appeared with a notable delay and reversed slowly. All blockers lengthened synaptic delay. When compared at approximately equipotent concentrations for potentiation of transmitter release, TEA and 4-AP were found to produce a similar lengthening of the synaptic delay whereas Cs+ caused a much greater prolongation. The quantal size of the fast excitatory postsynaptic potential and the amplitude of the acetylcholine potential were not affected by 4-AP or Cs+, but were depressed by TEA. These results indicate that TEA, 4-AP and Cs+ enhance evoked transmitter release in bullfrog sympathetic ganglia. It is suggested that the potentiation is caused, at least in part, by a mechanism that increases Ca++ influx in the nerve terminal. The enhanced influx is presumed to be mediated by a broadening of the presynaptic action potential after K+-channel blockade.

4-Aminopyridine↗
PubMed1984

Effects of Na+ gradient on the intracellular Ca2+ oscillation in the sympathetic ganglion cell: Na-Ca exchange in the neurone cell soma?

The effects of the removal of extracellular Na+ and the increase in the intracellular Na+ on the slow rhythmic membrane hyperpolarizations (rmhs) were studied in bullfrog sympathetic ganglion cells. The interval of rmhs, reflecting a relative change in the basal intracellular Ca2+, was lengthened by either treatment, disfavouring the possible involvement of the Na-Ca exchange mechanism in the Ca2+-buffering in the ganglion cell soma.

Animals↗
PubMed1984

(+)-Tubocurarine blocks the Ca2+-dependent K+-channel of the bullfrog sympathetic ganglion cell.

(+)-Tubocurarine [+)-Tc: 10-100 microM) reduced the duration of the afterhyperpolarization, which was induced by the activation of Ca2+-dependent K+-conductance (GK,Ca) following an action potential in the bullfrog sympathetic ganglion cell, but did not affect the maximum rates of rise and fall of Na+- and Ca2+-dependent action potentials. The amplitudes of slow rhythmic membrane hyperpolarizations produced by rhythmic rises in the GK,Ca were also decreased by (+)-Tc without a change in their intervals. Thus, (+)-Tc appears to block the Ca2+-dependent K+-channel of the bullfrog sympathetic ganglion cell.

Animals↗
PubMed1984

Restoration of the nicotinic receptor-channel activity from the blockade by atropine in bullfrog sympathetic ganglia.

Atropine (3 microM) reduced both the nicotinic and muscarinic acetylcholine (ACh) potentials of the bullfrog sympathetic ganglion cell. However, the former was completely restored within 1 h during a sustained exposure to atropine, while the latter remained blocked. Similar restorations were observed for the depressant effects on both the amplitude and decay phase of a nerve-induced postsynaptic current. The results suggest that the sustained or repetitive binding of atropine to this site results in a new conformational state capable of passing ions almost normally, but resistant to the blockade by atropine.

Acetylcholine↗
PubMed1984

Comparison of effectiveness of thyrotropin-suppressive doses of D- and L-thyroxine in treatment of hypercholesterolemia.

In an attempt to compare the cholesterol-lowering effects of equivalent doses of D- and L-thyroxine, 10 euthyroid, hypercholesterolemic subjects were treated with graded doses of each medication in a cross-over design using thyrotropin suppression following thyrotropin-releasing hormone administration as the end-point. The mean thyrotropin-suppressive dose of D-thyroxine was 2.4 +/- 0.66 mg per day, which resulted in mean reductions of 10 percent in total plasma cholesterol, 10 percent in plasma low-density lipoprotein cholesterol, and 11 percent in plasma high-density lipoprotein cholesterol. The mean thyrotropin-suppressive dose of L-thyroxine was 135 +/- 46 micrograms per day, which resulted in mean reductions of 7 percent in total plasma cholesterol, 6 percent in plasma low-density lipoprotein cholesterol, and 14 percent in plasma high-density lipoprotein cholesterol. The reductions in total, low-density, and high-density cholesterol achieved with D-thyroxine were not significantly different from those achieved with L-thyroxine. Neither medication produced a significant increase in heart rate or ventricular ectopy as determined by Holter monitoring. These data do not support the belief that D-thyroxine has a preferential cholesterol-lowering effect in humans when compared with equivalent doses of L-thyroxine. In addition, both D- and L-thyroxine reduced plasma high-density lipoprotein cholesterol.

Adult↗
PubMed1983

Does intracellular release of Ca2+ participate in the afterhyperpolarization of a sympathetic neurone?

The afterhyperpolarization (AHP) of an action potential in the bullfrog sympathetic ganglion cell was highly sensitive to anions (a factor affecting Ca2+ release) filled in a recording electrode; it was slower for citrate ion than for Cl-. The AHP recorded with a 'KCl-electrode' was suppressed drastically by D-600 (Ca2+-antagonist) and prolonged significantly by caffeine (promoting Ca2+ release), while the AHP recorded with a 'K3-citrate-electrode' was affected only slightly by these agents. Thus, these results suggest that Ca2+ entry during an action potential is the main origin of Ca2+ for the AHP recorded with a 'KCl-electrode', and favour the idea that the intracellular release of Ca2+ by an action potential as well as the Ca2+ influx participates in the mechanism of the AHP recorded with a 'K3-citrate-electrode'.

Action Potentials↗