The effects of temporal trachea-occlusion at the end of expiration on internal intercostal muscle activity (IIMA) and diaphragmatic activity (DMA) were studied in the vagi-intact rabbit. This tracheal occlusion caused a marked prolongation of inspiration time due to a diminution of the vagally mediated inspiratory inhibition but the significant change in the next IIMA was not observed after releasing tracheal occlusion. In addition, the effects of temporal trachea-occlusion on pulmonary stretch receptor activity (PSRA) and DMA were also studied in the unilaterally vagotomized rabbit. The procedures remarkably inhibited the respiratory modulation of PSRA from inspiration to expiration. These results indicate that the change of PSRA in response to temporal trachea-occlusion does not significantly affect the next IIMA.

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The purpose of this study was to investigate the differences in kinetics of CO₂ output (V_CO2) during incremental exercise in sprinters (S), middle (MD), and long distance runners (LD). In the steady state exercise, the V_CO2 was linearly related to the O₂ uptake (V_O2). In the incremental exercise below anaerobic threshold (AT), the V_CO2 was also linearly related to the V_O2. The difference between the V_CO2 estimates from the regression lines obtained in steady state and incremental exercise was added from the start of exercise up to a given time. The added values were defined as CO₂ stores. The CO₂ stores per body weight were significantly related to mixed venous CO₂ pressure (PV_CO2) determined by the CO₂ rebreathing method. The slopes of the regression lines between PV_CO2 and CO₂ stores per body weight were not different among three groups. If V_CO2 above AT is estimated from the VO₂ using the regression line obtained in incremental exercise below AT, the estimated V_CO2 is lower than the measured V_CO2. The sum of the differences in V_CO2 up to a given time was defined as CO₂ excess. The CO₂ excess per body weight was significantly related to ΔLA (the difference between blood lactates at 5min after exercise and at rest). The ratios of CO₂ excess per body weight to ΔLA were 3.30±1.49, 4.16±2.33, and 5.55±2.05 for sprinters, middle, and long distance runners, respectively. This ratio obtained in sprinters was significantly lower than that in long distance runners (p<0.01).

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The effects of the voltage-dependent Ca²⁺ inward current (I_Ca) on γ-aminobutyric acid (GABA)-induced Cl^- current (I_Cl) in isolated frog sensory neurones were examined using the "concentration clamp" technique, an approach which combines internal perfusion by a suction pipette with a rapid external solution change method. A preceding I_Ca suppressed the GABA-activated I_Cl. While the inhibition was not influenced by changes of membrane potential between -40 and -100mV, it was reduced when the internal EGTA concentration was increased. A preceding I_Ca shifted the GABA dose-response curve to the right without affecting the maximum current or the Hill coefficient (n=2). Inhibition of the GABA-activated I_Cl, by I_Ca showed a recovery in a single exponential manner, the time constant of which depended upon the extent of Ca²⁺ influx. At a low temperature (10°C), however, the recovery from Ca²⁺ - mediated inhibition was only slight. We conclude that, as a result of the voltage-dependent Ca²⁺ influx, a subsequent increase of intracellular Ca²⁺ concentration modulates the GABA-gated I_Cl in the soma membrane. Possible mechanisms are discussed.

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we studied the ionic mechanism of low resting potential (RP) of quiescent "diseased" human atrial fibers. The RP was -49.7±0.8mV (n=179) in normal Tyrode's solution (5.4mM [K]_o, 36°C). The changes in RP measured at various levels of [K]_o appeared to fit the RP-[K]_o relationship predicted by the Goldman-Hodgkin-Katz equation, assuming P_Na/P_K ratio (α) to be 0.102 and [K]_i to be 131.9mM. The α far exceeded the normal value (about 0.01) by a factor of 10. Acetylcholine (ACh, 10μM) led to marked increases in the RP. An application of tetrodotoxin (TTX, 6μM) and perfusion with low [Na]_o (10% of the control) media in the presence and absence of ACh produced considerable hyperpolarizations of the RP. These findings indicate that increased α value is due to a combination of decreased PK and increased PNa. Applications of ouabain (5μM) and a cooling procedure (12.3°C) depolarized the membrane, whereas epinephrine (1μM) hyperpolarized it. Transient hyperpolarization, which exceeded the steady state levels of RP at 5.4mM [K]_o, was observed with perfusing of 5.4mM [K]_o media following perfusion with K-free media. These findings suggest that electrogenic Na pump current plays a significant role in the maintenance of the RP. In conclusion, partial depolarization of "diseased" human atrial fibers was attributed to both decreases in membrane K+ conductance and increases in Na+ conductance. The electrogenic outward pump current seemed to protect the fibers from severe depolarization produced by the conductance abnormality (increased P_Na/P_K).

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Phosphorus nuclear magnetic resonance (³¹P NMR) was used to study energy metabolism in the rat mandibular gland. The gland was isolated, perfused arterially and set in the NMR tube. At rest, 7 resonance peaks were observed and 6 peaks identified from low field as: 1) sugar phosphates (SP) and nucleotide monophosphate (NMP), 2) inorganic phosphate (Pi), 3) creatine phosphate (PCr), 4) γ-nucleotide triphosphate (NTP) and β-nucleotide diphosphate (NDP), 5) α-NTP, α- NDP, NAD+, and NADH, 6) an unknown peak, and 7) β-NTP. From the results of high performance liquid chromatography (HPLC), NTP consisted mainly of ATP and GTP, and UTP was not detected. The tissue contents of ATP and GTP in the perfused gland were determined by HPLC as 1.86±0.03 and 0.37±0.01mmol/kg wet tissue (S.E., n=5). From ³¹P NMR and HPLC data, the tissue levels of creatine phosphate, ADP, and sugar phosphates were estimated as 3.3, 0.4, and 4.2mmol/kg wet tissue, respectively. The cessation of perfusion decreased the tissue levels of PCr and ATP and increased those of Pi and SP. On the other hand, administration of acetylcholine (1μM), which is an optimal dose for secretion, decreased PCr and increased Pi but did not change SP. The ATP was unchanged initially and slowly decreased to the lower level during sustained secretion. These findings suggest that a sustained secretion requires more energy from ATP hydrolysis rather than initial secretion.

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Blood flows in the finger were measured simultaneously by laser Doppler flowmetry and by venous occlusion plethysmography in a warm environment (35°C, 40% RH). One hand was immersed in a water bath the temperature of which (T_W) was raised every 10min by steps of 2°C from 35 to 43°C, while the other hand was kept immersed in water at 35°C. Finger blood flow in the heated hand (BF_w) measured with venous occlusion plethysmography was significantly lower than that in the control hand (BF_c) at T_w of 39-41°C. At T_w of 43°C, however, the finger BF_w returned to the level of BF_c after a transient decrease. In contrast, blood flow in the heated hand measured with laser Doppler flowmetry (LDF_w) increased steadily as the T_w was raised from 37 to 43°C, while that in the opposite hand (LDF_c) remained unchanged. Assuming that the laser Doppler flowmetry does not measure blood flow through AVAs located deeply in the skin of the finger but measures flow through the superficial capillaries, the results suggest that the decrease in finger blood flow in response to local heating may be limited to AVAs, and superficial vessels may not contribute to this heat-induced vasconstriction of the finger.

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The possible influence of neurogenic factors on respiratory and circulatory responses to continuous static (CSE), rhythmic static (RSE), and dynamic (DE) exercises was studied in 15 healthy young men. Ventilation (V_E), oxygen uptake (V_O2), cardiac output (Q), and blood pressure (BP) were measured during the steady-state of the exercise. For a given V_O2, V_E, and respiratory frequency (f) enhanced significantly with increasing frequency of RSE, and for the same frequency, the responses of these variables to RSE were significantly higher than those for DE. Although a similar trend was observed in heart rate (HR) and Q responses to exercises, it was not as strong as for ventilatory responses. These results lead to the conclusion that ventilation and circulation during exercise may be influenced by some neurogenic factors mediated either centrally or peripherally.

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To clarify the role of the carotid body in the mechanism governing exercise hyperpnea, the effect of hypoxia and hyperoxia on ventilation and cardiac output was studied in four healthy men. The VE increased 10.7% in hypoxia and decreased 10.1% in hyperoxia from normoxia as judged from the steady-state values during exercise. On the contrary, Q showed only a slight reduction of -3.2% in hyperoxia. The hypoxic hyperpnea and hyperoxic hypopnea led to a concomitant alteration in PET_CO2. An overshoot following the onset of exercise was observed during the first 30s of VE response in hypoxia, which dampe progressively in normoxia and hyperoxia. No remarkable difference was observed in the early transient responses of Q between hypoxia and hyperoxia. The discrepancy in the dynamics between VE and Q led to a phasic deviation in PET_CO2; an isocapnic transition from the control to stimulus period in normoxia, hypocapnic in hypoxia and hypercapnic in hyperoxia. The time constant representing the kinetics of VE and that for V_CO2 prolonged significantly in hyperoxia. These results support the cardiodynamic consequence of exercise hyperpnea, i.e., the carotid body is the first to respond to the increase in CO₂ flow into the lungs.

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The ionic mechanism of the effect of micropressure ejection of dopamine (DA) and forskolin on the membranes of identified inhibition of long duration (ILD) neurons of Aplysia kurodai was investigated with conventional voltage-clamp and ion-substitution techniques. Ejection of DA and forskolin onto the neuropil of the ILD neuron produced a slow outward current (5-20nA in amplitude; 10-60s in duration) associated with a conductance increase. The outward currents induced by DA and forskolin were consistently a linear function of the holding potential, reversing near the predicted potassium equilibrium potential (-80mV), and were sensitive to changes in the concentration of extracellular K⁺ but not to extracellular Cl^- Bath-applied isobutylmethylxanthine (50μM) prolonged the outward current induced by both DA and forskolin, but imidazole (5mM) had an opposite effect on these currents. Tolbutamide (1-5mM), a protein kinase inhibitor, reduced the current induced by both DA and forskolin. A antagonist for DA receptors in molluscan neuron, ergometrine maleate, (10μM) completely abolished the outward current induced by DA, but the current induced by forskolin persisted in the presence of the DA-antagonist. Guanosine 5′-O-(2-thiodiphosphate) (GDPβS, 5-10μM), an analogue of GDP inhibited the outward current induced by both DA and forskolin. These results suggest that dopamine acts on the ILD neurons of Aplysia kurodai by increasing K⁺ conductance. Forskolin can mimic the DA action, suggesting that the effect of dopamine is mediated by increased intracellular cAMP.

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Contribution of Ca²⁺-influx via the slow channel to generation of the transient inward current in guinea-pig ventricular muscles was studied using a single sucrose gap voltage clamp technique. The transient inward current (TI) was induced from superfusion of the preparations with the low-K⁺ (0mM), high-Ca²⁺ (3.6mM) solution. Application of 2mM-Co²⁺ quickly and reversibly suppressed the TI amplitude to 25% of the control and delayed its peak timing to 153% during 10-20min. Inhibition developed as quickly as Co²⁺ suppressed the slow inward current (I_s), and its recovery took place without apparent time lag behind its effect on I_s. The block of both TI and I_s by Co²⁺ was antagonized by raising external Ca²⁺ to 7.2mM. Removal of external Ca²⁺ caused a prompt suppression of both I_s and TI. Application of 2 or 5mM-procaine HCl produced a complete abolition of TI with a mild depression of I_s. While 1mM-caffeic caused a suppression of TI after a transient augmentation, 10mM-caffeine completely eliminated it without abolishing I_s. These results indicate that the Ca²⁺-influx through the slow channel acts not only to load the cell with those ions, but also to influence somehow the Ca²⁺-release from the stores under the Ca²⁺ -overloaded conditions.

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In smooth muscle cells of the rabbit basilar artery, field stimulation evoked a depolarizing response which consisted of a fast (1-3s duration) and a following slow (1-4min duration) component. The amplitude of these responses increased in an intensity-dependent manner and, when exceeding 10-15mV, a spike potential was generated. During generation of the slow depolarization, ionic conductances of the membrane were increased. When outward current pulses with long duration (2-3s) were applied to the smooth muscle using the partition stimulating method, electrotonic potentials and spike potentials were generated. The cessation of the current pulse caused repolarization of the membrane with time constant of 250-350ms. The depolarizing responses were resistant to tetrodotoxin, sympathetic transmission blocking agents (guanethidine, bretylium, or 6-hydroxydopamine treatment), receptor antagonists for 5-hydroxytryptamine (methysergide), dopamine (haloperidol), ACh (atropine), noradrenaline (phentolamine), ATP (α, β-mATP) or histamine (mepyramine), blockade of synthesis of prostaglandins or thromboxane A₂ (indomethacin) or high Mg²⁺, low Ca²⁺ solution. Smooth muscle cell membrane of the basilar artery was depolarized by 5-hydroxytryptamine (above 0.1μM) or histamine (above 10μM) but not by ACh (up to 100μM) or noradrenaline (up to 10μM). The depolarization induced by 5-hydroxytryptamine or histamine was antagonized by methysergide or mepyramine, respectively. Denervation of the vessel by storing in a cold condition (4°C) decreased but did not abolish the depolarizing response. The decrease in amplitude of the depolarizing response during cold storage was attributed to associated depolarization of the smooth muscle membrane. Internal perfusion of the vessel with distilled water abolished generation of the depolarizing response, and this procedure also abolished the endothelium-dependent relaxation induced by ACh during the potassium contraction. The results suggest that the depolarizing response evoked by field stimulation is generated by substances released from non-neural components, possibly from the endothelial cells.

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The contractile response of the myometrial longitudinal muscle of pregnant and estrogen-treated rats to adenosine triphosphate (ATP) was investigated. ATP (10^-5-4×10^-3M) added to Krebs solution caused a generation of spontaneous activity consisting of phasic contractions and an elevation of muscle tone in a dose-dependent manner. Effects of the "test solution" consisting of isotonic K, 4(mM) ATP, 4Mg, 1-20 EGTA, 20 tris(hydroxymethyl)aminomethan (Tris) maleate (pH 6.8) on the contractile response was then investigated. An initial phasic and a following tonic contraction was evoked by the application of the test solution, when applied after the equilibration of the muscle with Krebs solution. ATP was proved to be an agonist to evoke the Ca-free contraction. The phasic contraction was depressed when the muscle was incubated with Ca-free Krebs solution. The amplitude of the tonic contraction became progressively larger when application of the test solution was repeated. The amplitude was 15-70% as large as the tonic component of the K-contracture induced by 40mM K. Theophylline (10mM), 0.1mM papaverine and 1μM isoprenaline nearly abolished, and 1mM cAMP partly depressed the tonic contraction of K-contracture, whereas the tonic contraction induced by the test solution was unaffected. A calmodulin antagonist, W-7 (100μM) strongly suppressed both the K-contracture and the contraction induced by the test solution, whereas trifluoperazine (10-200μM) preferentially depressed the K-contracture. The tonic contraction induced by the test solution was strongly depressed when Mg was removed and 20mM EDTA was applied. From these results, it is discussed that some Ca-independent process is involved in the generation of tonic component of Ca-free contraction developed by the application of the test solution.

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The arsenazo III Ca²⁺-transients (AZ signals) were measured in hypertonic solution. The muscle fiber of Xenopus was stimulated at the frequency of 0.1/s. The AZ signal responding to the first stimulus in hypertonic Ringer solution was nearly similar to that in normal Ringer solution. After 8 repetitive stimuli, however, time to peak was increased to 3 times and decay time constant was up to 4 times as long as the control. The apparent inhibition of Ca²⁺ uptake into sarcoplasmic reticulum was supposed to be the origin of the prolongation in time to peak and decay time course.

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Using a new X-ray TV system, we studied the effects of metabolic acidosis, produced by intravenous injection of lactic acid, on internal diameter (ID; 100-500μm), flow velocity, and volume flow in pulmonary microcirculation of anesthetized cats. We found that metabolic acidosis decreased the ID of arteries by 21%, whereas it increased flow velocity by 28% but not volume flow.

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The amplitude of acetylcholine (ACh)-induced contraction of isolated rat ileum was enhanced at medium temperatures lower than normal body temperature. Maximum enhancement was achieved between 30 and 25°C. Changes in medium pH and activities of the enteric nervous system due to temperature changes were not essential for this enhancement.

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A neuropeptide Phe-Met-Arg-Phe-NH₂ (FMRFamide) induces K⁺-dependent outward current in Aplysia neurons. Intracellular application of islet activating protein (TAP) irreversibly and selectively blocked this outward current without affecting resting membrane conductance. An injection of GTPγS, a nonhydrolyzable analogue of guanosine triphosphate (GTP), caused very slow irreversible increase in K⁺-conductance of the resting membrane. However, repetitive applications of FMRFamide significantly expedited the effect of GTPγS. These results strongly suggest that K⁺-channel opening induced by FMRFamide is regulated by an IAP-sensitive GTP-binding protein.

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