The existence of thermoregulatory nonshivering thermogenesis, with special reference to lipid metabolism, was investigated in men. Acute cold exposure (10°C, 60 min) produced a marked increase in heat production, with concomitant elevation of plasma free fatty acid (FFA) level, modest increase of ketone body concentration and lowered respiratory quotient (R.Q.). The correlation of heat production to plasma FFA levels was significantly positive; that is, subjects with higher heat production showed higher plasma FFA levels. Moreover, correlation of either heat production or plasma FFA levels to R.Q. was significantly negative, respectively. On the other hand, exposure to cold after an administration of nicotinic acid, which has a suppressive effect on FFA mobilization from adipose tissue, resulted in less cold-elevated heat production, a significant fall of plasma FFA and ketone body concentrations, and no change in R.Q. Although no visible or only slight shivering was observed in control cold exposure study, greater shivering occurred in the nicotinic acid cold exposure study.
These results appear to indicate that nonshivering thermogenesis as a source of heat production achieved by enhanced utilization of lipids is also present in men.

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Transmembrane resting potentials of squid axons were measured with variation of intracellular salt concentrations. It was found that the dependence of resting potential on the extracellular K-ion concentration was practically unaffected by the change of ionic strength in the intracellular phase, and the relationship of membrane potential and the logarithm of extracellular K-ion concentration was a straight line with a slope of about 50 mV/10-fold extracellular K-ion concentration. Also, the degree of change in resting potential due to the change of intracellular K-ion concentration was not affected appreciably by the extracellular solution with various K-ion concentrations, and the membrane potentials were insensitive over a wide range of intracellular K-ion concentrations.
It was also indicated that the observed transmembrane potentials are not explained by a conventional membrane potential theory.

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By using a gradient layer calorimeter built in our laboratory, heat balance during physical restraint was measured in rats at a calorimeter temperature of 25°C. After restraint, the rate of heat production (M) increased sharply and significantly (from 53.86 W ·m^-2±3.12 SE to 69.12 W ·m^-2+2.86 SE). The high M was maintained for the whole period of 2.5-hr restraint. The rate of heat loss (H_L) increased progressively and reached a high value (from 54.02 W ·m^-2 ±2.78 SE to 67.44 W ·m^-2±2.48 SE) 40 min after restraint. The high value in EL was maintained (67.44-68.12 W ·m-2) and the rate of heat storage (S), which was positive during the first 40 min, tended toward zero for the rest of 2.5-hr restraint. Colonic temperature (T_col), which was increased from 37.40 °C ±0.07 SE to 38.03 °C ±0.16 SE during the first 40 min, increased insignificantly during the following period of restraint. These results indicated that a thermal equilibrium was reached during a prolonged restraint at a calorimeter temperature of 25 °C. After release from restraint, H_L and M decreased progressively. S, which was negative in the first 60 min of post-restraint period, became zero and T_col reached a steady value of 37.78°C±0.09 SE.
The restraint-hypermetabolism was either reduced or completely inhibited by the chemical sympathectomy (6-OHDA, 100 mg/kg i.p.) or bilateral adrenalectomy. An increased activity of the sympathetic nervous system and an increased secretion of catecholamines might be responsible for the restraint-hypermetabolism in rats.
This report has also described a direct calorimeter for measuring heat balance in unanesthetized rats. The results obtained in this study approved the simplicity of the actual operation and the usefulness of the calorimeter in studying thermoregulatory responses in small mammals.

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Antagonistic action of caffeine and adenosine were studied at the membrane current and tension component levels in myocardium of the bullfrog atrium, mainly under voltage clamp using the double sucrose-gap method.
Caffeine (1-5 mM) produced marked augmentation of the phasic and tonic tensions as well as slow inward current (I_s). At higher concentrations it elicited an increase of the delayed outward current (I_x). The augmentation of Is was principally due to increase of the limiting conductance (g_s), while the activation and inactivation variables (d∞, f∞) were not changed significantly. The dose-tension response curve for caffeine, which appeared sigmoidal, was notably lowered in the presence of adenosine (1-3 mM), indicating a competitive type of inhibition. Adenosine, in the presence of caffeine, exerted a narcotic-like action by inhibiting all of the membrane currents (I_Naf, I_s, I_x and background inward current, I_b) and tension components (I_ca-dependent and independent tensions). The inhibition of I_s was due to a decrease of gs and no appreciable change was observed in d∞ and f∞. These results suggest that adenosine has a strong stabilizing action on the myocardium, especially when the heart muscle activity is accelerated by increased cyclic AMP.

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Membrane electrical properties of the clonal anterior pituitary cell (GH₃) were studied using intracellular recording techniques. The resting potential in the GH₃cell was -48.0±1.1 mV (mean±S.E., n=39) in normal saline. The input resistance estimated from the linear portion of the current-voltage relationship was 453±30 MΩ(n=21). The maximum rate of rise of the action potential was 7.0±1.1 V/sec (n=12) at room temperature (23-25°C). The action potential had both Na and Ca components. The Ca component was abolished by addition of 4 mm Co²⁺. Sr²⁺ could substitute for Ca²⁺in supporting spike initiation. As the concentration of Sa²⁺ was increased, the maximum rate of rise of the action potential increased. After replacement of Ca²⁺with isomolar Ba2+ the membrane potential shifted to -6.1±1.1 mV (n=11). In the Ba solution, prolonged action potentials were evoked by a depolarizing current pulse after maintaining the membrane potential more negative than -50 mV. The release of both prolactin and growth hormone was enhanced by increasing the external K+ concentration to 50 mm in the presence of Ca²⁺. Sr²⁺could substitute for Ca²⁺. Ba²⁺enhanced the release of both hormones, even if the K+ concentration was unaltered. The facilitatory effects of high K⁺ and Ba²⁺were markedly suppressed by addition of 2-4 mm Co²⁺. These results may suggest that the potential-dependent increase in the membrane permeability to Ca²⁺, responsible for initiation of the Ca spike, plays a significant role in stimulation of hormone secretion in GH3 cells.

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To make clear the control mechanism of force generation in human muscle, the electrical activity of the brachialis muscle was studied at various levels of contraction force by recording single motor unit discharges as well as mass electromyograms (EMGs).
The firing rate of motor units increased with force along an S-shaped curve. At low levels of force, motor units increased their firing rates steeply with force. At intermediate levels of force, each motor unit increased its firing rate linearly with force at lower rates. As the maximum of force was approached, the firing rate increased very steeply, reaching as high as 50 Hz or more.
By applying a new method of statistical processing to mass EMGs, the number of active motor units and the size of action potential were estimated at each level of force. The number of active motor units increased monotonously with muscle force. Motor units recruited at high levels of force had larger amplitudes of action potentials than those recruited at lower levels.
Calculations were made to determine how the relative contribution to an increase in muscle force is varied between recruitment and the increase in firing rate. The contribution of recruitment gradually decreased with the increase in force. Up to about 70% of the mixmum force, recruitment is the major mechanism for increasing the force of contraction.

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Bevelled glass microelectrodes were used to record spike potentials extracellularly from the ganglion cells of the rabbit retina. Good responses were obtained from the isolated retina or eye-cup preparation for at least 12 hr. Using a contrast reversal stimulus, 63.8 (67/105) of the units showed linear spatial summation (X-cells), and 21.0 %(22/105) showed nonlinear spatial summation (Y-cells). The Xand Y-cells in the rabbit retina had physiological properties which were similar to those in cat retina. Directionally selective cells (15.2 %) were found to respond poorly, if at all, to the contrast reversal stimulus.

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The effects of various cations on the water unit activity were studied by recording unitary discharges in the superior laryngeal nerve fibers of the rabbit. Chloride salts of Li⁺, Na⁺, K⁺, Cs⁺ depressed the water response, while sulfate salts of Li⁺, Na⁺, NH₄⁺, K⁺ facilitated it. Cations were less effective in stimulating action than anions. The depression of the water response in the laryngeal nerve has been thought to be caused by permeation of the stimulating anions through the receptor membrane and/or by destruction of the water structure on the membrane surface induced by adsorbed anions (SHINGAI, 1977 a). In order to differentiate these two possible actions of anions, the effects of benzenesulfonate and trichloroacetate were examined, because these anions were expected to be impermeant through the receptor membrane and to have a water structure-breaking effect. These anions showed no effect on the water response in concentrations below 320 mM. Measurements of the viscosity and the density of the electrolyte solutions showed that benzenesulfonate had a strong water structure-breaking effect. These results suggested that impermeant anions having water structure-breaking actions do not influence the excitability of the water receptor and that the depression of the water response by anions in the stimulating solution is caused by a hyperpolarization generated by permeation of the anions through the receptor membrane.

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Many neurons in the inferior dorsolateral area of the monkey prefrontal cortex showed sustained increases in discharge rates during continuous gazing at a tiny light spot that had a reward significance. These increases might depend upon stimulus factors (light target), behavioral factors (gazing) or both. In this report, we tried to separate these factors and to test the extent to which each factor might contribute to the neuronal reaction.
Monkeys were trained to exhibit two kinds of behavior: 1) maintained gazing at a light target and 2) “gazing” behavior without a clear target.We then examined neuronal behavior in these two k inds of gazing behavior. During “gazing at target, ” many prefrontal neurons showed tonic activation ; thus the previous findings were confirmed. The seneurons b ehaved in various ways in “gazing without target”: 1) some of the neurons were activated to the same extent as in “gazing at target”; 2) many others also showed activation but with lower discharge rates;and 3) the rest of the neurons completely ceased activation.
Such variation in discharge patterns may be interpreted as meaning that there is a continuous and graded difference among individual neurons in the dependence of their gaze-related activation upon a visible target. Then it seems that the stimulus factors are involved in a graded manner in generation of the activation, and further that other factors, probably behavioral ones, also contribute in part to it.

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In dog submandibular glands, we measured changes in metabolic heat production during a secretory period which was induced by electrical stimulation of the chorda tympani. When measured with fine thermocouples, the temperature of both the gland itself and venous blood from the gland increased by 0.1-0.7°C at the maximum. The blood flow was about 0.3 g·min^-1·g^-1 wet weight of gland at a resting period and increased to 1-3 g·min^-1·g^-1 at the maximum of secretory response. The resting heat production in vitro, measured by a microcalorimeter, was 3.3 mW·g^-1 at 27°C and 7.8 mW·g-1 at 37°C. The specific heat of the blood and the salivary gland, measured by a microcalorimeter, were 3.97 and 3.91 J-1·°C-1, respectively. The change in conductive heat loss, measured by a thermopile under stimulated conditions, ranged from 4 to 6 mW·g-1 at the maximum. Metabolic heat production during secretion in vivo (37°C) was estimated from temperature changes in the glandular tissue and blood, blood flow, specific heat and resting heat production. Values obtained were in the range from 15 to 80 mW·g-1 at the maximum. Heat production increased rapidly within the first 20 sec to reach a maximum and then declined with time, but slow heat production continued. On the basis of the present results together with those from former studies on ionic transport in the salivary gland, we discussed the relation of heat production to transport of substances during secretory processes.

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