쥐 척수후각세포의 유해자극 반응에 대한 칼슘이온통로 차단제의 억제작용

강석한,김기순,신홍기,Kang, Sok-Han,Kim, Kee-Soon,Shin, Hong-Kee 대한약리학회 1997 The Korean Journal of Physiology & Pharmacology Vol.1 No.6

Calcium ions are implicated in a variety of physiological functions, including enzyme activity, membrane excitability, neurotransmitter release, and synaptic transmission, etc. Calcium antagonists have been known to be effective for the treatment of exertional angina and essential hypertension. Selective and nonselective voltage-dependent calcium channel blockers also have inhibitory action on the acute and tonic pain behaviors resulting from thermal stimulation, subcutaneous formalin injection and nerve injury. This study was undertaken to investigate the effects of iontophoretically applied $Ca^{++}$ and its antagonists on the responses of WDR (wide dynamic range) cells to sensory inputs. The responses of WDR cells to graded electrical stimulation of the afferent nerve and also to thermal stimulation of the receptive field were recorded before and after iontophoretical application of $Ca^{++}$, EGTA, $Mn^{++}$, verapamil, ${\omega}-conotoxin$ GVIA, ${\omega}-conotoxin$ MVIIC and ${\omega}-agatoxin$ IVA. Also studied were the effects of a few calcium antagonists on the C-fiber responses of WDR cells sensitized by subcutaneous injection of mustard oil (10%). Calcium ions and calcium channel antagonists ($Mn^{++}$, verapamil, ${\omega}-conotoxin$ GVIA & ${\omega}-agatoxin$ IVA) current-dependently suppressed the C-fiber responses of WDR cells without any significant effects on the A-fiber responses. But ${\omega}-conotoxin$ MVIIC did not have any inhibitory actions on the responses of WDR cell to A-fiber, C-fiber and thermal stimulation. Iontophoretically applied EGTA augmented the WDR cell responses to C-fiber and thermal stimulations while spinal application of EGTA for about $20{\sim}30\;min$ strongly inhibited the C-fiber responses. The augmenting and the inhibitory actions of EGTA were blocked by calcium ions. The WDR cell responses to thermal stimulation of the receptive field were reduced by iontophoretical application of $Ca^{++}$, verapamil, ${\omega}-agatoxin$ IVA, and ${\omega}-conotoxin$ GVIA but not by ${\omega}-conotoxin$ MVIIC. The responses of WDR cells to C-fiber stimulation were augmented after subcutaneous injection of mustard oil (10%, 0.15 ml) into the receptive field and these sensitized C-fiber responses were strongly suppressed by iontophoretically applied $Ca^{++}$, verapamil, ${\omega}-conotoxin$ GVIA and ${\omega}-agatoxin$ IVA. These experimental findings suggest that in the rat spinal cord, L-, N-, and P-type, but not Q-type, voltage-sensitive calcium channels are implicated in the calcium antagonist-induced inhibition of the normal and the sensitized responses of WDR cells to C-fiber and thermal stimulation, and that the suppressive effect of calcium and augmenting action of EGTA on WDR cell responses are due to changes in excitability of the cell.

암모니아가 가토심방근 및 동방결절세포의 활동전압에 미치는 효과

조용수,강석한,김진혁,고상돈,김기순,Cho, Yong-Soo,Kang, Sok-Han,Kim, Jin-Hyuk,Koh, Sang-Don,Kim, Kee-Soon 대한생리학회 1989 대한생리학회지 Vol.23 No.2

Electrophysiological effects of ammonia was studied in the isolated superfused sinus node and atrial muscle cells of the rabbit heart. No significant changes were observed in the overshoot potential (05), maximum diastolic potential (MDP), and action potential amplitude (APA) of the sinus node cells following superfusion with 3.0 mM ammonia, fifty times upper limit of the normal human plasma level. However the action potential duration (APD) of sinus node cells were significantly prolonged after superfusion with 0.6 mM ammonia for 20 min or with 1.2 and 3.0 mM ammonia for 5 minutes. Ammonia in all the concentrations tested decreased the rate of spontaneous firing (RSF) from the sinus node cells. After superfusion of sinus node cells with 0.3 mM ammonia for 20 min, the RSF significantly decreased from 20 min to 25 min after onset of superfusion while a significant decrement in the RSF was observed from 7 min to 30 min following superfusion with 3.0 mM ammonia for S min. On the other hand, the effects of ammonia on the action potential of the rabbit atrial muscle cell were much similar to those on pacemaker cells except that the atrial cell was generally less sensitive to ammonia. The results suggest that ammonia may cause changes in the action potential of the rabbit cardiac cells by the direct action, and that the cardiac effects of ammonia are generally opposite to those of glycine.

Taurine 및 ${\beta}-alanine$이 고양이 척수후각세포의 Activity에 미치는 효과

고영익,강석한,김진혁,신홍기,김기순,Koh, Young-Ik,Kang, Sok-Han,Kim, Jin-Hyuk,Shin, Hong-Kee,Kim, Kee-Soon 대한생리학회 1990 대한생리학회지 Vol.24 No.1

In 19 cats anesthetized with ${\alpha}-chloralose$ effects of taurine and ${\beta}-alanine$ on the responses of wide dynamic range (WDR) cells to mechanical, chemical and thermal stimuli were investigated in the lumbar spinal cord of the cat. Also studied was an interaction of strychnine with taurine in affecting the activities of WDR cells. Following intravenous administration of taurine, the responses of WDR cells to all types of mechanical stimuli were markedly enhanced, demonstrating that the response to pressure was most sensitive to taurine action. When the receptive field was exposed to thermal stimuli ($50^{\circ}C$) for 20 sec. taurine increased activity of WDR cell to 169.5% of the control value. The $K^{+}$-induced activation of WDR cells was invariably suppressed after taurine administration. Intravenously administered strychnine remarkably reduced the enhanced response of WDR cell to natural stimuli resulting from intravenous administration of taurine. Also ${\beta}-alanine$ markedly activated the response of spinal dorsal horn cell to natural mechanical stimuli. These findings suggest that neutral amino acid and its derivative such as ${\beta}-alanine$ and taurine can enhance the response of WDR cells to different stimuli in cats.

Taurine 및 ß-alanine이 고양이 척수후각세포의 Activity에 미치는 효과

고영익(Koh, Young-Ik),강석한(Kang, Sok-Han),김진혁(Kim, Jin-Hyuk),신홍기(Shin, Hong-Kee),김기순(Kim, Kee-Soon) 대한생리학회 1990 대한생리학회지 Vol.24 No.1

In 19 cats anesthetized with α-chloralose effects of taurine and β-alanine on the responses of wide dynamic range (WDR) cells to mechanical, chemical and thermal stimuli were investigated in the lumbar spinal cord of the cat. Also studied was an interaction of strychnine with taurine in affecting the activities of WDR cells. Following intravenous administration of taurine, the responses of WDR cells to all types of mechanical stimuli were markedly enhanced, demonstrating that the response to pressure was most sensitive to taurine action. When the receptive field was exposed to thermal stimuli (50℃) for 20 sec. taurine increased activity of WDR cell to 169.5% of the control value. The K⁺-induced activation of WDR cells was invariably suppressed after taurine administration. Intravenously administered strychnine remarkably reduced the enhanced response of WDR cell to natural stimuli resulting from intravenous administration of taurine. Also β-alanine markedly activated the response of spinal dorsal horn cell to natural mechanical stimuli. These findings suggest that neutral amino acid and its derivative such as β-alanine and taurine can enhance the response of WDR cells to different stimuli in cats.

Sprague-Dawley계 정상 흰쥐에서 위점막 알코올 탈수소효소 활성에 대한 성별의 영향

성기철 ( Ki Chul Sung ),강주섭 ( Ju Seop Kang ),이창호 ( Chang Ho Lee ),고현철 ( Hyun Chul Koh ),신인철 ( In Chul Shin ),강석한 ( Sok Han Kang ),전용철 ( Yong Chul Jeon ),엄애선 ( Ae Son Om ) 한국응용약물학회 2000 Biomolecules & Therapeutics(구 응용약물학회지) Vol.8 No.1

수종 염증반응매개물질이 피부염에 의한 척수후각세포의 activity변동에 미치는 효과

강석한,김기순,손진식,김진혁 한양대학교 의과대학 1990 한양의대 학술지 Vol.10 No.1

In order to investigate the effects of inflammatory mediators on theelectrophysiological characteristics of the dorsal horn cells in the inflammatory-induced animal, activities of these cells to mechanical stimuli were recorded before and after intravenous administration of cyproheptadine, indomethacin and clonidine to the cat with carrageenin-induced inflammation. The results obtained can be summarized as follows: 1) Following inductions of a cutaneous inflammation the activities of wide dynamic range (WDR) cell, high threshold (HT) cell and low threshold (LT) cell as well were greatly enhanced. 2) In the inflammation-induced animals an enhanced activities of LT cell to brush was not affected by indomethacin or clonidine, but the response to squeeze which was usually not appeared in normal animals was suppressed markedly by intravenously administered indomethacin. 3) Each one of the intravenously administered cyproheptadine (2mg/kg), indomethacin (5mg/kg) and clonidine (50μg/kg) significantly suppressed the activated responses of HT cells to pressure or squeeze in the cat with carrageenin-induced inflammation. 4) the enhanced activity of WDR cell due to the cutaneous inflammation was also remarkably inhibited after separate intravenous administration of cyproheptadine, indomethacin and clonidine and the response to squeeze was affected more strongly thanthat to brush. 5) The expanded receptive field of HT cells resulting from inflammation was abolished after intravenous administration of cyproheptadine, indomethacin and clonidine. The results of present study suggest that in the animal with carrageenin-induced inflammation, the WDR and HT cells could be activated by the direct and/or the sensitizing actions of inflammatory mediators.

말초신경손상에 의한 척수감각신경 세포의 감작

강석한,김찬,엄민숙,김진혁,김기순 한양대학교 의과대학 1997 한양의대 학술지 Vol.17 No.1

Peripheral nerve injuries have been known to result in a chronic neuropathic pain characterized by symptoms of spontaneous burning pain, hyperalgesia, and allodynia. Recently it has been reported that the flexor reflex was greatly enhanced immediately after peripheral nerve section in the experimental animals. The persent study was underaken to investigte acute effects of the peripheral nerve injury on the sensitization of dorsal hom cells. After the sciatic nerve section, neither significant change was observed in the wind-up of WDR cells, nor wind-up was produced in the WDR cell that had not shown wind-up before the afferent nerve section. The A-fiber responses of WDR cells were not altered after section of the sciatic nerve. However, the C-fiber responses and after-discharge of the dorsal horn cell to imput signals started to increase in 2 hours after the nerve section. In 70% of experimental animals, the nerve section-induced increments in the WDR cell activities were abolished after topical application of 2% lidocaine to the proximal end of cut sciatic nerve. After pretreatemnt of the experimental animals with a NMDA receptor blocker, MK-801, the C-fiber response and after-discharge of the dorsal horn cell well not changed by the sciatic nerve section. These findings suggest that peripheral injury induces the sensitization of dorsal horn cells of the spinal cord and that signals from the proximal stump is essential for maintenance of the sensitization, which was mediated by NMDA receptors.

Glycine이 적출 정상 및 자발성 고혈압 백서 대동맥 평활근의 수축성에 미치는 효과

강석한,신태순,고상돈,김기순 한양대학교 의과대학 1992 한양의대 학술지 Vol.12 No.1

Glycine has been known to possess significant cardiovascular effects. Electrophysiological effects of glycine were demonstrated in the rabbit sinus node cells. Recently it was also reported that glycine induced endothelium-dependent contractions in the isolated rabbit aorta. On the other hand, it has been generally agreed that the vascular reactivity was also altered in spontaneously hypertensive rats(SHR). The present study was performed to investigate effects of glycine on the vascular smooth muscle in the 16 week old Wistar-Kyoto rats(WKY) and in the age-matched SHR. The systolic pressures of WKY and SHR were 123.9±9.4mmHg and 198.5±8.5mmHg, respectively. Glycine(10-100mM) produced endothelium-dependent contractions in the isolated aortic rings of both WKY and SHR. At concentration of 50mM glycine increased vascular tension respectively by 60.2±6.9%(percentage to contraction induced by 1×10 M) and 89.4±2.9% in WKY and SHR. After denudation the vascular responmses to 50mM glycine solution were respectively 25.4±1.8 and 34.2±1.4% in WKY and SHR. Also hyperosmolarity provoked vascular contractions. Following superfusion with 370mOsm Krebsmannitol solution which ws equimolar with 50mM glycine solution, vascular tension increased by 24.5±4.7% in both animal groups. The results indicate that glycine may produce endothelium-dependent contractions in the isolated aorta of SHR, and that vascular responses to glycine are more sensitive in SHR.

Arginine이 가토 심방근 수축력 및 동방결절세포의 전기생리학적 특성에 미치는 효과

김기순,강석한,고상돈,김진혁 한양대학교 의과대학 1991 한양의대 학술지 Vol.11 No.2

In other to explore effects of arginine, one of the basic amino acid on the cardiac function, changes in atrial contractility and action potentials of the sinus noed cells were determined in the isolated rabbit heart following superfusion with Tyrode's solution containing different amount of arginine. After superfusion with arginine (30mM) the amplitued of action potential (APA) of the sinus node cells generally decreased as a result of a greater decrement in maximum diastolic potential (MDP) than a simultaneous increment of avershoot potential (OS). No sigvificant changes were observed in action potential duration (APD) and rate of spontaneous firing (RSF) of the sinus node cells after superfusion with arginine solutions. At low concentration (3-6mM) arginine decreased atrial contractility while at high concentration (30mM) an initial positive inofropic response (between 3 and 5 min after onset of superfusion )was followed by a negative response. On the other hand, arginine intensified the initial positive inotropic response induced by reducing stimulation frequency of the atrial segment from 2Hz to 0.5Hz. And the negative inotropic effect of arginine (6mM) was abolished in the rabbir atrial segment pretreated with caffeine. The results of present study suggest that arginine can act diretly on the cardiac cells of rabbir heart resulting in an alteration lf transmenbrane potential and atrial contractility.

사람의 제대혈관 장력에 미치는 DMSO(Dimethyl Sulfoxide)의 효과

김상재,강석한,정인덕,김기순 한양대학교 의과대학 1998 한양의대 학술지 Vol.18 No.2

Starting from 1960s through to 1980s, dimethyl sulfoxide (DMSO) earned fame as a valuable agent that could be used for many purposes including patient therapy. DMSO is dipolar aprotic compound endowed with unique physical and chemical properties. It is a potent solvent for a broad spectrum of solutes. DMSO has been known to exert varions biological effects such as diuretic, vasodilatory, analgesic, anti-inflammatory and cardiovascular effects. Also DMSO has been reported to reduce intracranial pressure and improve cerebral blood flow in experimentally induced ischemia and vasospasm. Some studies presented a possibility that may alter vascular smooth muscle tension. On the other hand, human umbilical vessels are ideal for the study of vasoactive substances because of poor innervation of autonomic nerves to umbilical vessels. This study was undertaken to investigate effects of DMSO on the vascular tension of human umbilical vein (HUV) and artery (HUA). DMSO(1-10%) relaxed HUV and HUA preparations precontracted with KCl (3×10^-2M) in a concentration-dependent manner. At all concentrations, vasodilating effect of DMSO was greater in HUV than HUA. Pretreatment with methylene blue (5×10^-6M), soluble guanylate cyclase inhibitor and L-NAME (10^-4M), NO synthase inhibitor, did not alter relaxing action of DMSO. After pretreament with indomethacin, cyclooxygenase inhibiotor, the DMSO-induced relaxing response was partially suppressed only in HUA (41 ± 5.7%). Following chemical denudation with saponin (0.03mg/ml, 45min), the DMSO-induced relaxing responses of both umbilical vessels were not changed. These results suggest that the DMSO induces an endothelium-independent relaxation both in the human umbilical artery and vein, and that the DMSO-induced relaxing response of HUA results, at least in part, from the mediation of prostanoids.