• The Korean Journal of Physiology and Pharmacology
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• 제12권5호
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• pp.267-274
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• 2008

Since first discovered in chick skeletal muscles, stretch-activated channels (SACs) have been proposed as a probable mechano-transducer of the mechanical stimulus at the cellular level. Channel properties have been studied in both the single-channel and the whole-cell level. There is growing evidence to indicate that major stretch-induced changes in electrical activity are mediated by activation of these channels. We aimed to investigate the mechanism of stretch-induced automaticity by exploiting a recent mathematical model of rat atrial myocytes which had been established to reproduce cellular activities such as the action potential, $Ca^{2+}$ transients, and contractile force. The incorporation of SACs into the mathematical model, based on experimental results, successfully reproduced the repetitive firing of spontaneous action potentials by stretch. The induced automaticity was composed of two phases. The early phase was driven by increased background conductance of voltage-gated $Na^+$ channel, whereas the later phase was driven by the reverse-mode operation of $Na^+/Ca^{2+}$ exchange current secondary to the accumulation of $Na^+$ and $Ca^{2+}$ through SACs. These results of simulation successfully demonstrate how the SACs can induce automaticity in a single atrial myocyte which may act as a focus to initiate and maintain atrial fibrillation in concert with other arrhythmogenic changes in the heart.

• International Journal of Oral Biology
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• 제43권4호
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• pp.209-216
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• 2018

Reactive oxygen species (ROS) and nitrogen species (RNS) are involved in cellular signaling processes as a cause of oxidative stress. According to recent studies, ROS and RNS are important signaling molecules involved in pain transmission through spinal mechanisms. In this study, a patch clamp recording was used in spinal slices of rats to investigate the action mechanisms of $O_2{^{{\bullet}_-}}$ and NO on the excitability of substantia gelatinosa (SG) neuron. The application of xanthine and xanthine oxidase (X/XO) compound, a ROS donor, induced inward currents and increased the frequency of spontaneous excitatory postsynaptic currents (sEPSC) in slice preparation. The application of S-nitroso-N-acetyl-DL-penicillamine (SNAP), a RNS donor, also induced inward currents and increased the frequency of sEPSC. In a single cell preparation, X/XO and SNAP had no effect on the inward currents, revealing the involvement of presynaptic action. X/XO and SNAP induced a membrane depolarization in current clamp conditions which was significantly decreased by the addition of thapsigargin to an external calcium free solution for blocking synaptic transmission. Furthermore, X/XO and SNAP increased the frequency of action potentials evoked by depolarizing current pulses, suggesting the involvement of postsynaptic action. According to these results, it was estblished that elevated ROS and RNS in the spinal cord can sensitize the dorsal horn neurons via pre- and postsynaptic mechanisms. Therefore, ROS and RNS play similar roles in the regulation of the membrane excitability of SG neurons.

• Korean Circulation Journal
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• 제53권4호
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• pp.239-250
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• 2023

Background and Objectives: Brugada syndrome (BrS) is an inherited arrhythmia syndrome that presents as sudden cardiac death (SCD) without structural heart disease. One of the mechanisms of SCD has been suggested to be related to the uneven dispersion of transient outward potassium current (I_to) channels between the epicardium and endocardium, thus inducing ventricular tachyarrhythmia. Artemisinin is widely used as an antimalarial drug. Its antiarrhythmic effect, which includes suppression of I_to channels, has been previously reported. We investigated the effect of artemisinin on the suppression of electrocardiographic manifestations in a canine experimental model of BrS. Methods: Transmural pseudo-electrocardiograms and epicardial/endocardial transmembrane action potentials (APs) were recorded from coronary-perfused canine right ventricular wedge preparations (n=8). To mimic the BrS phenotypes, acetylcholine (3 μM), calcium channel blocker verapamil (1 μM), and I_to agonist NS5806 (6-10 μM) were used. Artemisinin (100-150 μM) was then perfused to ameliorate the ventricular tachyarrhythmia in the BrS models. Results: The provocation agents induced prominent J waves in all the models on the pseudo-electrocardiograms. The epicardial AP dome was attenuated. Ventricular tachyarrhythmia was induced in six out of 8 preparations. Artemisinin suppressed ventricular tachyarrhythmia in all 6 of these preparations and recovered the AP dome of the right ventricular epicardium in all preparations (n=8). J wave areas and epicardial notch indexes were also significantly decreased after artemisinin perfusion. Conclusions: Our findings suggest that artemisinin has an antiarrhythmic effect on wedge preparation models of BrS. It might work by inhibition of potassium channels including I_to channels, subsequently suppressing ventricular tachycardia/ventricular fibrillation.

• The Korean Journal of Physiology
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• 제18권1호
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• pp.19-35
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• 1984

Since the first report of Drury and $Szent-Gy{\ddot{o}}rgyi$ in 1929, the inhibitory influences of adenosine on the heart have repeatedly been described by many investigators. These studies have shown that adenosine and adenine nucleotides have overall depressant effects, similar to those of acetylcholine. Heart beats become slow and weak. It is also well known that adenosine is a potent endogenous coronary vasodilator. Many investigations on the working mechanisms of adenosine have been focused mainly on the effects of the coronary blood flow. However, the cellular mechanisms underlying the inhibitory action of adenosine on sinus node are not well understood yet. Thus, this study was undertaken to examine the behavior of rabbit SA node under influence of adenosine. In these series of experiments three kinds of preparations were used: whole atrial pair, left atrial strip, and isolated SA node preparations. The electrical activity of SA node was recorded with conventional glass microelectrodes 30 to 50 $M{\Omega}$. The preparations were superfused with bicarbonate-buffered Tyrode solution of pH 7.35 and aerated with a gas mixture of $3%\;CO_2-97%\;O_2$ at $35^{\circ}C$. In whole atrial pair, adenosine suppressed sinoatrial rhythm in a dose-dependent manner. Effect of adenosine on atrial rate appeared at the concentration of $10^{-5}M$ and was enhanced in parallel with the increase in adenosine concentration. Inhibitory action of adenosine on pacemaker activity was more prominent in the preparation pretreated with norepinephrine, which can steepen the slope of pacemaker potential by increasing permeability of $Ca^{+2}$. Calcium ions in perfusate slowly produced a marked change in sinoatrial rhythm. Elevation of the calcium concentration from 0.3 to 8 mM increased the atrial rate from 132 to 174 beats/min, but over 10 mM $Ca^{+2}$ decreased. The inhibitory effect of adenosine on sinoatrial rhythm developed very rapidly. Atrial rate was recovered promptly from the adenosine-induced suppression by the addition of norepinephrine, but extra $Ca^{+2}$ was less suitable to restore the suppression of atrial rate. Adenosine suppressed also atrial contractility in the same dosage range that restricted pacemaker activity, even in the reserpinized preparation. In isolated SA node preparation, spontaneous firing rate of SA node at $35^{\circ}C$(mean{\pm}SEM, n=16) was $154{\pm}3.3\;beats/min. The parameters of action potentials were: maximum diastolic potential(MDP), $-73{\pm}1.7\;mV: overshoot(OS), $9{\pm}1.4\;mV: slope of pacemaker potential(SPP), $94{\pm}3.0\;mV/sec. Adenosine suppressed the firing rate of SA node in a dose-dependent manner. This inhibitory effect appeared at the concentration of $10^{-6}M$ and was in parallel with the increase in adenosine concentration. Changes in action potential by adenosine were dose-dependent increase of MDP and decrease of SPP until $10^{-4}M$. Above this concentration, however, the amplitude of action potential decreased markedly due to the simultaneous decrease of both MDP and OS. All these effects of adenosine were not affected by pretreatment of atropine and propranolol. Lowering extra $Ca^{2+}$ irom 2 mM to 0.3 mM resulted in a marked decrease of OS and SPP, but almost no change of MDP. However, increase of perfusate $Ca^{2+}$ from 2 mM to 6 or 8 mM produced a prominent decrease of MDP and a slight increase of OS and SPP. Dipyridamole(DPM), which is known to block the adenosine transport across the cell membrane, definately potentiated the action of adenosine. The results of this experiment suggest that adenosine suppressed pacemaker activity and atrial contractility simultaneously and directly, by decreasing $Ca^{2+}-permeability$ of nodal and atrial cell membranes.

• Toxicological Research
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• 제22권1호
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• pp.23-30
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• 2006

Among poly aromatic hydrocarbons, dioxin and PCBs are the most controversial environmental pollutants in our modern life. These pollutants are known as human carcinogens, and liver is the most sensitive target in animal cancer models. Specific aims of the study were focused on the mechanism of carcinogenesis in hepatocytes and the structure-activity relation among these diverse environmental chemicals. Because key mechanisms of dioxin-induced carcinogenesis in human epithelial cell model are the alteration of signal transduction pathway and PKC isoforms, the alteration of the signal transduction pathways and other factors associated with carcinogenesis were studied. Rat hepatocytes cultured under the sandwich protocols were exposed with the various concentration of dioxins and PCBs, and signal transduction pathway, protein kinase C isoforms, oxidant stress, and apoptotic nuclei were evaluated. Since it is important to understand the structure-activity relation among these chemicals to properly assess the carcinogenic potentials, the study analyzed the parameters associated with carcinogenic processes, based on their structural characteristics. In addition, signal transduction pathways and PKC isoforms involved in inhibition of UV-induced apoptosis were also analyzed to elaborate the tumor promotion mechanism of these chemicals. Induction of apoptosis by UV irradiation was optimal at $60\;J/m^2$ in primary hepatocyte in culture. Compared to non coplanar PCBs such as PCB 114 and PCB 153, coplanar PCBs such as PCB 77 and PCB126 showed a stronger inhibition of apoptosis induced by UV irradiation. Production of reactive oxygen species (ROS) was more stimulated by non-coplanar PCBs than coplanar PCBs with the most potent induction of ROS by chlorinated non-coplanar PCB. As compared to the level of induction by PCB126, non-coplanar PCB153 showed a higher increase of intracellular concentrations. Besides the alteration of intracellular calcium concentration, translocation of PKC from cytosolic fraction to membrane fraction was clearly observed upon the exposure of non-coplanar PCB. Taken together, the present study demonstrated that there is a potent structure-activity relationship among PCB congeners and the mechanism of PAH-induced carcinogenesis is structure-specific. The study suggested that more diverse pathways of PAH-induced carcinogenesis should be taken into account beyond the boundary of Ah receptor dogma to assess the health impact of PAH with more accuracy.

• Molecules and Cells
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• 제20권3호
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• pp.315-324
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• 2005

Pain is an unpleasant sensation experienced when tissues are damaged. Thus, pain sensation in some way protects body from imminent threat or injury. Peripheral sensory nerves innervated to peripheral tissues initially respond to multiple forms of noxious or strong stimuli, such as heat, mechanical and chemical stimuli. In response to these stimuli, electrical signals for conducting the nociceptive neural signals through axons are generated. These action potentials are then conveyed to specific areas in the spinal cord and in the brain. Sensory afferent fibers are heterogeneous in many aspects. For example, sensory nerves are classified as $A{\alpha}$, $-{\beta}$, $-{\delta}$ and C-fibers according to their diameter and degree of myelination. It is widely accepted that small sensory fibers tend to respond to vigorous or noxious stimuli and related to nociception. Thus these fibers are specifically called nociceptors. Most of nociceptors respond to noxious mechanical stimuli and heat. In addition, these sensory fibers also respond to chemical stimuli [Davis et al. (1993)] such as capsaicin. Thus, nociceptors are considered polymodal. Recent advance in research on ion channels in sensory neurons reveals molecular mechanisms underlying how various types of stimuli can be transduced to neural signals transmitted to the brain for pain perception. In particular, electrophysiological studies on ion channels characterize biophysical properties of ion channels in sensory neurons. Furthermore, molecular biology leads to identification of genetic structures as well as molecular properties of ion channels in sensory neurons. These ion channels are expressed in axon terminals as well as in cell soma. When these channels are activated, inward currents or outward currents are generated, which will lead to depolarization or hyperpolarization of the membrane causing increased or decreased excitability of sensory neurons. In order to depolarize the membrane of nerve terminals, either inward currents should be generated or outward currents should be inhibited. So far, many cationic channels that are responsible for the excitation of sensory neurons are introduced recently. Activation of these channels in sensory neurons is evidently critical to the generation of nociceptive signals. The main channels responsible for inward membrane currents in nociceptors are voltage-activated sodium and calcium channels, while outward current is carried mainly by potassium ions. In addition, activation of non-selective cation channels is also responsible for the excitation of sensory neurons. Thus, excitability of neurons can be controlled by regulating expression or by modulating activity of these channels.

• 한국식품저장유통학회지
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• 제21권4호
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• pp.460-467
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• 2014

혼합야채추출물의 항산화와 ${\alpha}$-amylase 및 ${\alpha}$-glucosidase 억제활성 증진을 위해서 톳, 매생이, 미역귀의 첨가효과를 분석하였으며 해조류 첨가된 야채추출물의 일반성분과 미네랄 함량 변화를 조사하였다. 3가지 해조류의 첨가량은 야채추출물의 일반성분에 유의적으로 영향을 미치지 않은 반면 톳과 미역귀 5% 첨가에 의해 칼슘, 나트륨, 칼륨, 마그네슘, 철분 함량이 유의적으로 증가하였다. 톳 20% 첨가한 경우 총 폴리페놀 함량과 환원능력이 야채추출물보다 각각 47.08와 16.82%로 유의적으로 증가하였다. 반면에 3가지 해조류 첨가에 의한 hydroxyl radical 소거활성이 큰 변화가 없었다. 톳, 매생이, 미역귀 20% 첨가에 의해 DPPH radical 소거활성이 각각 27.47, 22.25, 17.27%로 유의적으로 증가하였다. 해조류 첨가된 혼합 야채 추출물이 상대적으로 약한 ${\alpha}$-amylase 억제활성을 지니고 있는 동시에 강한 ${\alpha}$-glucosidase 억제활성이 나타냈다. 특별히 미역귀 5% 첨가한 경우 ${\alpha}$-glucosidase을 98.26%로 유의적으로 억제하였다. 전반적으로 해조류 첨가를 통해 야채추출물의 미네랄 함량이 증가하였고 항산화와 2형 당뇨병 관련 효소 억제활성이 개선됨을 알 수 있었다.

• 청정기술
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• 제24권1호
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• pp.41-49
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• 2018

$25^{\circ}C$에서 $CO_2$ 흡착을 위한 작업용량과 $CO_2/CO$ 선택계수를 현저하게 향상시키기 위하여 서로 다른 전하와 이온반경을 갖는 $Na^+$, $N^+$, $Ca^{2+}$와 $Cu^{2+}$로 이온교환된 Y 제올라이트들이 연구되었다. 매우 소량인 0.012% $Ca^{2+}$로 이온교환된 NaY는 7회의 반복적인 $CO_2$ 흡착/탈착 싸이클 동안에도 완전히 가역적이었으므로 기존에 보고된 것들과는 달리 표면에 카보네이트는 생성되지 않는 것으로 생각된다. 4 bar 이상에서 2.00% CaY, 1.60% CuY와 1.87% LiY 모두 NaY와 매우 유사한 $CO_2$ 흡착성능을 보였다할지라도 그보다 낮은 압력에서는 이들의 흡착능은 감소하였고 그 정도는 금속이온들의 종류에 의존하였다. 0.5 ~ 2.5 bar에서 $CO_2$ 흡착성능은 NaY > 1.60% CuY > 2.00% CaY > 1.87% LiY의 순으로 나타났는데, 이들 모두 동일한 faujasite 골격과 약 2.6의 Si/Al 비율을 가지므로 골격, 골격조성, 유효세공크기와 채널구조에 있어서 차이는 없기 때문에 약한 루이스산의 특성을 갖는 $CO_2$의 구별되는 흡착거동은 이온교환에 따른 국부염기도와 흡착 포텐셜 에너지의 변화 때문일 것이다. $CO_2$ 흡착과는 다른 경향성이 CO 흡착에서 나타났고 이는 보다 약한 사극자 상호작용 때문이다. 0.012 ~ 5.23% Ca 함량을 갖는 Y 제올라이트에 $CO_2$와 CO 흡착 시 Ca 함량에 따른 현저한 의존성이 존재하였는데 0.05% 이하에서 $CO_2$ 흡착능은 증가한 반면에 그 이상에서는 감소하였다. 이러한 경향에도 불구하고 Ca 함량의 증가와 함께 작업용량과 $CO_2/CO$ 선택계수는 현저히 증가하였고, 5.23% CaY의 경우 작업용량은 $2.37mmol\;g^{-1}$, 선택계수는 4.37이었는데 본 연구에서 얻어진 작업용량은 문헌에 보고된 벤치마크와 유사한 수준이었다.

• 자원환경지질
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• 제28권3호
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• pp.185-197
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• 1995

충주 광산 지역은 계명산층과 이를 관입한 중생대 화강암질 암석으로 구성되며, 이들 화강암질 암석중 백악기초(134 Ma) 흑운모 화강암과 계명산층을 구성하는 석영-운모 편암의 접촉부에서 회중석을 수반하는 스카른 광상이 산출된다. 스카른은 구성광물의 공생 특성과 주 구성광물의 양적인 비에 의해 석류석 스카른대, 규회석 스카른대, 녹염석 스카른대 및 녹니삭 스카른대로 분류된다. 석류석의 화학조성은 초기 순수한 안드라다이트 (>Ad96)에서 후기 알루미늄 함량비가 증가하는 안드라다이트-그라슈라(Ad~50)로 점이적인 변화를 나타내며, 녹염석은 $Fe^{3+}$ 의 함량비가 높은 고용체 상(Ps=35)에서 암루미늄 함량비가 높은 고용체 상(Ps=25)으로 변화하는 양상을 띤다. 광물 공생 및 화학 조성상의 특징으로 볼 때 스카른화 작용은 Ca와 Fe의 활동도가 흑운모 화강암의 접촉부에서 높고 Al, Mg, K 및 Si 활동도는 석영-운모 편암내에 발달되는 스카른에서 증가하는 경향을 나타낸다. 녹염석 스카른대에서 산출되는 회중석의 유체포유물 균질화 온도는 $300{\sim}380^{\circ}C$ 이며 NaCl 상당 염농도는 3-8wt. %로, 석영 및 녹염석 유세포유물 균질화 온도는 $300{\sim}400^{\circ}C$이다. 후기 녹니석 스카른대내에서 수반되는 황화광물의 황 동위원소비는(${\delta}^{34}S$) 황철석 $9.13{\sim}9.51%_{\circ}$, 방연석 $5.85{\sim}5.96%_{\circ}$이며, 공존하는 황철석-방연석 광물쌍에 의한 동위 원소 지질온도는 $283{\pm}20^{\circ}C$이다. 이산화탄소 몰분율($X_{CO_2}$)은 $L-CO_2$가 관찰되지 않으며 $H_2O$ 풍부한 유체포유물로 구성되고 있는점과, 안드라다이트 및 규회석의 광물공생 특성과 대비하여 볼때 약 0.01로 추정된다. 광물공생 및 화학조성, 상 안정 관계, 유체포유물 연구, 동위원소 지질온도계등의 연구 결과에 의해 충주광산 지역 스카른화 작용은 $400{\sim}260^{\circ}C$ 온도 조건과 산소분압이 감소($fo_2=10^{-30}{\sim}10^{-25}$)하는 환경에서 진행되었으며, 텅스텐 광화작용은 이러한 스카른 형성 과정 중 온도의 감소($350^{\circ}C$)와 산소분압이 감소($fo_2=10^{-27}$) 하는 조건에서 수반되었다.

• The Korean Journal of Physiology
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• 제21권2호
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• pp.241-257
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• 1987

The effects of external $Ca^{2+}$ and $Ca^{2+}-antagonists$ on the spontaneous contractions and electrical activities were investigated in guinea-pig stomach in order to clarify the mechanism for the generation of slow waves. Electrical responses of circular smooth muscle cells were recorded using glass capillary microelectrodes filled with 3 M KCl. All experiments were performed in tris-buffered Tyrode solution which was aerated with 100% $O_2$ and kept at $35^{\circ}C$. The results obtained were as follows: 1) The amplitude of spontaneous contractions was maximal at around 2-4 mM $Ca^{2+}$, whereas their frequency was inversely related with external $Ca^{2+}$ within the range of 0.5 to 16 mM $Ca^{2+}$. 2) Verapamil suppressed the amplitude of spontaneous contraction in a dose-dependent manner, while the frequency of spontaneous contractions was almost not changed over the whole concentration of verapamil $(0.01{\sim}5\;mg/l)$. 3) Manganese increased both the amplitude and the frequency of spontaneous contractions dose-dependently in low $Mn^{2+}$ (below 0.05 mM $Mn^{2+}$), while their amplitude and frequency were decreased in high $Mn^{2+}$ (above 0.1 mM $Mn^{2+}$). 4) The ampltude and maximum rate of rise of slow waves were incrased in high $Ca^{2+}$ solution. In $Ca^{2+}-free$ solution, the spontaneous contractions recorded simultaneously with slow waves ceased and tonic contraction ($Ca^{2+}-free$ contracture) was developed in parallel with membrane depolarization and the disappearance of slow waves. 5) Verapamil (1 mg/1) decreased the amplitude and maximum rate of rise of slow waves and it depolarized the membrane by about 6 mV, whereas the frequency of slow waves was not affected by verapamil. 6) Manganese showed different characteristic effects between low and high $Mn^{2+}$ on the slow waves: In low $Mn^{2+}$ (0.05 mM $Mn^{2+}$), the initial rapid increases and the subsequent gradual decreases in three parameters of slow waves (amplitude, rate of rise, and frequency of slow waves) till a new steady state were observed. However, in high $Mn^{2+}$ (0.5 mM $Mn^{2+}$) slow waves disappeared and membrane was depolarized. From the above results, the following conclusions could be made: 1) $Ca^{2+}$ is necessary for a generation of the slow waves, even though it is small amount. 2) Verapamil suppresses the spontaneous contractions of gastric antral strip by the decreases in amplitude and maximum rate of rise of slow waves, while this drug does not block the $Ca^{2+}-channel$ involved in the generation of slow waves. 3) Manganese has dual actions on the $Ca^{2+}-channels$; the $Ca^{2+}-channel$ involved in the generation of slow waves (or Na-Ca exchange system) or the channel for the generation of spike potentials are stimulated by a low concentration of $Mn^{2+}$, while both the $Ca^{2+}$. Channels are blocked by high concentration of $Mn^{2+}$.