The effects of hypertonic solution on action potential and input resistance were studied using the guinea-pig ventricular muscle. Hypertonic solutions containing excess (150 and 300mOsm/liter) sucrose, glucose, NaCl, Na₂SO₄, or LiCl produced a prolongation of action potential duration (APD) followed by a gradual shortening. These solutions increased the input resistance of the preparation. The prolongation of APD began immediately after the onset of perfusion with hypertonic solution and peaked within about 10min, while the late shortening of APD developed progressively. On introducing the isotonic solution after the osmotic challenge, APD initially shortened and then gradually prolonged toward the control level. Slightly hypertonic solutions containing excess 30 or 75mM sucrose prolonged APD, to some extent. It is concluded that the hypertonic solution exerts early and late effects on APD in guinea-pig ventricular muscle. The early effect, which is responsible for the APD prolongation, seems to be directly related to the development of cell dehydration. The hypertonic solutions produced a slight increase in the resting potential, and sucrose- and glucose-hypertonicity depressed the rising phase of the action potential. These effects can be explained by the cell dehydration and associated changes in the intracellular ion concentrations. The increase in input resistance produced by hypertonic solutions was accompanied by an enhanced spatial decay of electrotonic potentials along the muscle bundle, as determined by the two microelectrode method, suggesting that the electrical resistance of the internal current pathway increases under hypertonic conditions.

View full abstract

When the guinea-pig ventricular muscle was exposed to hypertonic solution, duration of the action potential (APD) initially increased and then progressively decreased. To inverstigate the mechanism underlying this phenomenon, the preparations were perfused with the hypertonic solution under various experimental conditions. At low stimulus rates (0.1-l/min), the initial prolongation of APD was prominent while the later shortening of APD developed slowly, thereby suggesting that the effect of hypertonic solution on APD is dependent on the muscle activity. A pronounced shortening of APD occurred when the osmotic challenge was made at reduced [K]_o (2mM-K), at reduced [Na]_o (50%-Na), and at elevated [Ca]_o (5.4mM-Ca). Lowering the temperature from 36 to 26-27°C nearly abolished the development of APD shortening. The resting potential and the maximum rate of rise (V_max) of the action potential changed little even when APD was rapidly shortened during the osmotic challenge. Thus, the mechanism of APD shortening is thought to be independent of the factors determining the resting potential and V_max. Mn ions (1-2mM), verapamil (5-10μM), and Ba ions (0.05-0.2mM) had no effect on the hypertonicity-induced changes in APD. In partially depolarized preparations, hypertonic solution increased the duration of Ca-dependent slow action potentials without producing any parallel increase in their upstroke velocity. It is postulated that the initial prolongation of APD in response to hypertonicity is a direct result of cell dehydration. The later shortening of APD is probably derived from certain changes in the cell condition which developed secondarily to the cell dehydration. In these changes in APD, the slow Ca current seems to play a small role.

View full abstract

A dose of FOY-305 [N, N-dimethylcarbamoylmethyl-4-(4-guanidinobenzoyloxy) phenylacetate methanesulfonate; 100mg/kg body weight] was administered orally once a day for 30 days to a group of rats (FOY group). To the control group of rats, 10ml/kg body weight of distilled water (a solvent of FOY-305) was administered in the same way. The FOY-305 administration induced hypertrophy of the pancreas: the increase in wet weight of the pancreas was significantly higher than the increase in DNA content. The administration also induced hyperpyknia in the FOY group as shown by the increased concentration of constituents (amylase, trypsinogen, and chymotrypsinogen) in the pancreas.
The secretory responses of the exocrine pancreas to stimulation with cholecystokinin (CCK) were examined in vivo. The secretory responses induced by lowered doses of CCK in the FOY group were slightly greater than those in the control group, but the differences were not statistically significant. On the other hand, the responses induced by higher doses of CCK were significantly greater than those in the control group. The secretory responses to stimulation with CCK or acetylcholine (ACh) were examined further in vitro using an isolated perfused pancreas. Protein output induced by lower doses of the secretagogues (146-730pM CCK or 10nM ACh) was similar in the control and the FOY groups, but the output induced by higher doses of the secretagogues (1, 460pM CCK or 30-100nM ACh) in the FOY group was significantly larger than that in the control group.
The present results provided evidence that the FOY-305-induced hypertrophy and hyperpyknia of the rat pancreas coincided with potentiation of secretory responses to higher doses of the secretagogues.

View full abstract

1. Synaptic inputs of rubrospinal (RN) neurons from the cerebral cortex, pretectal area (PRT), and medial lemniscus (ML) were investigated electrophysiologically in the cat.
2. Stimulation of the ipsilateral parietal association cortex (PASC) and secondary sensory area (S_II) produced slow-rising about 3msec rise time monosynaptic EPSPs which were, in some cases, followed by hyperpolarizations, similar to the sensorimotor cortex (SM)-induced PSPs previously observed. Stimulation of the contralateral cerebral cortex never produced detectable PSPs.
3. Topographical arrangement of PASC-rubral projection was found. Stimulation of the lateral part of PASC induced EPSPs predominantly in RN cells innervating the cervicothoracic spinal segments, while stimulation of the medial part of PASC produced EPSPs predominantly in RN cells innervating the lumbosacral cord. Furthermore, PASC-induced EPSPs were more frequently recorded at the rostral half of RN than at the caudal half.
4. Monosynaptic EPSPs and multisynaptic IPSPs were induced by stimulation of the ipsilateral PRT and ML. PRT- and ML-induced EPSPs had times-to-peak of 1.0±0.4msec (mean±S.D.) and 1.6±0.5 msec, respectively, which were intermediate to those of the cerebral peduncle (CP)- and nucleus interpositus of the cerebellum (IP)-induced EPSPs. Furthermore, sensitivity of amplitudes of PRT-induced EPSPs to membrane hyperpolarization was intermediate to those of CP- and IP-EPSPs, and that of ML-induced EPSPs was lower than that of IP-EPSPs. Therefore, it is likely that synapses of PRT and ML fibers are formed between the distal dendrites where CP-rubral synapses terminate and soma where IP-rubral synapses terminate.
5. PASC-induced EPSPs after chronic IP and SM lesions had a new fast-rising component and the effectiveness of ML stimulation to induce the unit spike of RN cells was clearly increased in IP and SM lesioned cats. It was suggested that PASC-rubral fibers sprouted and formed new synapses at the proximal portions of soma-dendritic membranes of RN cells after IP and SM destructions. Collateral fibers to RN cells of the pyramidal tract were also shown to sprout new synapses following IP and ML lesions.

View full abstract

In view of the discrepancies in reports about the cerebral responses induced by stimulation of the cerebellar fastigial nucleus in the cat, attempts were made to re-evaluate the effects of stimulation of the fastigial nucleus in the cerebral cortex and thalamus of cats anesthetized with pentobarbital. Stimulation of the fastigial nucleus elicited responses of low amplitude bilaterally in the medial portion of the precruciate cortex in 7 out of 25 animals studied. The responses were mainly composed of a positive wave which reversed its polarity at a depth between 250 and 500μm from the cortical surface. Presumable relay cells for the responses were detected in the ventromedial nucleus and the medial area of the ventrolateral nucleus of the thalamus. Thalamic neurones showed a tendency to repetitive spike generation with variable latencies after fastigial stimulation, while conditioning stimuli applied to the midbrain reticular formation apparently counteracted it, enhancing the probability of generation of a single spike at a shorter latency. The effect of pentobarbital anesthesia on the fastigio-thalamic transmission is discussed in relation to the inconstant appearance of cortical responses after fastigial stimulation.

View full abstract

EEG spikes and their intracellular correlates were studied in both normal and kindled hippocampi (i.e., the hippocampi subjected to daily electrical stimulation) of rabbits. Many of the EEG spikes observed were referred to as inhibitory EEG spikes, because their intracellular correlates were hyperpolarizations of pyramidal cells. In most cases, these hyperpolarizations occurred without any preceding spikes, but could be led by a single spike. They were, however, never preceded by a spike burst. Inhibitory EEG spikes occurred in both normal and kindled hippocampi. In both cases, they not only appeared spontaneously, but were also induced by brain stem stimulation. Regardless of whether they appeared spontaneously or were induced by stimulation, the inhibitory EEG spikes and the corresponding hyperpolarizations were much larger in magnitude in the kindled than in the normal hippocampus. Consequently, it was concluded that enhancement of inhibition was one of the features of the kindled hippocampus.

View full abstract

The reflex control of gastric motility induced by chemical stimulation to a canine gastric mucosa was electromyographically studied in anesthetized dogs. In splanchnicectomized dogs, the instillation of 5ml of HCl solution with various pHs (pH 1-4) evoked a decrease in electrical control activity (ECA) frequency in accordance with stimulus strength. These responses were abolished by cervical or thoracic vagotomy. These results indicate that both afferent and efferent limbs of the reflex are in the vagus nerves. The results of alkaline stimulation was different from those of acidic stimulation. Decreasing response of ECA frequency following alkaline stimulation was completely abolished after the vagotomy similar to the acidic stimulation. On the other hand, the duration of the decreasing response to alkaline stimulation recovered faster than the response to acidic stimulation in the splanchnicectomized dogs. These results indicate that splanchnic nerves are contributing to the long lasting response to alkaline stimulation but not to that in acidic stimulation. The present experiment shows that the ECA frequency decreased after the acidic stimulation. When the stomach was filled with foods, the gastric pH may lower. Thus, decrease in ECA frequency after the acidic stimulation seems to play a physiological role of gastric contraction after feeding.

View full abstract

Locations and response characteristics of nociceptive neurons in the dorsal horn of the spinal cord were studied in urethane-chloralose anesthetized Japanese macaques. There were two general categories of nociceptive neurons. Neurons of the first type, nociceptive specific (NS) neurons, responded only to intense mechanical stimuli. Neurons of the second type, wide dynamic range (WDR) neurons, were activated by touch and pressure but responded maximally to noxious mechanical stimuli. NS neurons were located in laminae I and II_o of the superficial dorsal horn. WDR neurons were located not only in laminae I and II_o but also in laminae IV-VI. NS and WDR neurons in laminae I and II_o were spatially not segregated from each other. Projecting neurons were included in both categories of nociceptive neurons, but lamina II_o neurons were exclusively non-projecting neurons. Noxious heat stimulation of the peripheral receptive field as defined by mechanical stimuli, activated a significant fraction of NS and WDR neurons. Nearly all heat-sensitive WDR neurons in both the superficial layers and nucleus proprius received combined Aδ- and C-fiber input. Heat-sensitive NS neurons received either exclusively Aδ-fiber input or combined Aδ- and C-fiber input. All the heat-sensitive neurons tested showed a monotonous increase of heat-evoked discharges between the threshold temperature and the peak temperature. In both categories of heat-sensitive neurons, noxious heat neurons predominated over warming-noxious neurons. Hence, the thermal threshold did not necessarily parallel the mechanical threshold.

View full abstract

The effect of acute hyperthermia on circulatory function was studied in 6 mongrel dogs. At a core temperature of about 40°C, central venous pressure and stroke volume were maintained at almost normal level. Cardiac output significantly increased (26ml/(kg•min)) while systemic vascular resistance significantly decreased (1.2mmHg• sec/ml). In addition, significant decrease in vascular compliance by 40% was observed. When body temperature was raised further (severe hyperthermia), an abrupt fall of arterial pressure was observed at the rectal temperature of about 41-42°C. Concomitant decreases in central venous pressure (3mmHg), stroke volume (2.1ml/beat) and cardiac output (29ml/(kg•min)) were observed while heart rate increased (48 beats/min). These results suggest that the decrease in cardiac output during severe hyperthermia is due to the fall of central venous pressure, and the fall was attributed to the increase in unstressed vascular volume of systemic circulation due to the heat-induced cutaneous vasodilation. The observed decrease in systemic vascular compliance is considered to have a significant role in the maintenance of central venous pressure under hyperthermia.

View full abstract

The ionic mechanisms of the slow surface positive (P)-potential and the slow inhibitory postsynaptic potential (IPSP), an intracellularly recorded P-potential in sympathetic ganglia, were analysed by means of sucrose-gap, intracellular microelectrode techniques, and voltage clamp technique. Both the P-potential and the slow IPSP consist of two different potential components, namely the ouabain-sensitive and the ouabain-insensitive components. The ouabain-sensitive component was enhanced by a moderate conditioning hyperpolarization. This component was most reasonably explained as a potential change generated by an activation of the elctrogenic Na⁺ pump. The ouabain-insensitive potential component of the P-potential and the slow IPSP decreased in the amplitude and finally reversed its polarity by conditioning hyperpolarization. The reversal potential of ouabain-insensitive component of slow IPSP and slow inhibitory postsynaptic current (IPSC) was close to the E_K. The amplitude of ouabain-insensitive component of P-potential and slow IPSP was markedly decreased by an elevation of external K⁺ concentration. The reversal potential of ouabain-insensitive component shifted to a more positive potential level in high K⁺ Ringer's solution. On the other hand, it was augmented in K⁺-free Ringer's solution. A reduction of the membrane resistance was observed during the generation of the slow IPSP, when the membrane potential of ganglion cells was held at a membrane potential level more negative than -60mV. The slow IPSC recorded by voltage-clamp method was associated with an increase in membrane conductance. It was concluded that the ouabain-insensitive component was generated by an activarion of K⁺ conductance.

View full abstract

Vasoactive intestinal peptide (VIP) stimulated the pituitary-adrenocortical secretion following injection into the lateral ventricle of rats, but this effect was selectively inhibited by simultaneous administration of cholecystokinin octapeptide (CCK-8), but not by caeruletide.

View full abstract

The frontal cortex concerned with eye movements was investigated by electrical stimulation in the cat. Stimulation of the lateral part of the frontal cortex at the coronary sulcus evoked rapid medial movement and enophthalmos of the contralateral eye. The latency of eye movement following cortical stimulation was found to be shorter in the coronary sulcus than in the medial wall of the hemisphere under the cruciate sulcus or in the presylvian sulcus.

View full abstract