• The Korean Journal of Physiology and Pharmacology
• /
• 제15권6호
• /
• pp.415-422
• /
• 2011

Previously, we reported that besides retinal ganglion cell (RGC) spike, there is ~10 Hz oscillatory rhythmic activity in local field potential (LFP) in retinal degeneration model, rd1 mice. The more recently identified rd10 mice have a later onset and slower rate of photoreceptor degeneration than the rd1 mice, providing more therapeutic potential. In this study, before adapting rd10 mice as a new animal model for our electrical stimulation study, we investigated electrical characteristics of rd10 mice. From the raw waveform of recording using $8{\times}8$ microelectrode array (MEA) from in vitro-whole mount retina, RGC spikes and LFP were isolated by using different filter setting. Fourier transform was performed for detection of frequency of bursting RGC spikes and oscillatory field potential (OFP). In rd1 mice, ~10 Hz rhythmic burst of spontaneous RGC spikes is always phase-locked with the OFP and this phase-locking property is preserved regardless of postnatal ages. However, in rd10 mice, there is a strong phase-locking tendency between the spectral peak of bursting RGC spikes (~5 Hz) and the first peak of OFP (~5 Hz) across different age groups. But this phase-locking property is not robust as in rd1 retina, but maintains for a few seconds. Since rd1 and rd10 retina show phase-locking property at different frequency (~10 Hz vs. ~5 Hz), we expect different response patterns to electrical stimulus between rd1 and rd10 retina. Therefore, to extract optimal stimulation parameters in rd10 retina, first we might define selection criteria for responding rd10 ganglion cells to electrical stimulus.

• The Korean Journal of Physiology and Pharmacology
• /
• 제13권6호
• /
• pp.443-448
• /
• 2009

For successful visual perception by visual prosthesis using electrical stimulation, it is essential to develop an effective stimulation strategy based on understanding of retinal ganglion cell (RGC) responses to electrical stimulation. We studied RGC responses to repetitive electrical stimulation pulses to develop a stimulation strategy using stimulation pulse frequency modulation. Retinal patches of photoreceptor-degenerated retinas from rd1 mice were attached to a planar multi-electrode array (MEA) and RGC spike trains responding to electrical stimulation pulse trains with various pulse frequencies were observed. RGC responses were strongly dependent on inter-pulse interval when it was varied from 500 to 10 ms. Although the evoked spikes were suppressed with increasing pulse rate, the number of evoked spikes were >60% of the maximal responses when the inter-pulse intervals exceeded 100 ms. Based on this, we investigated the modulation of evoked RGC firing rates while increasing the pulse frequency from 1 to 10 pulses per second (or Hz) to deduce the optimal pulse frequency range for modulation of RGC response strength. RGC response strength monotonically and linearly increased within the stimulation frequency of 1~9 Hz. The results suggest that the evoked neural activities of RGCs in degenerated retina can be reliably controlled by pulse frequency modulation, and may be used as a stimulation strategy for visual neural prosthesis.

• The Korean Journal of Physiology
• /
• 제18권1호
• /
• pp.9-17
• /
• 1984

The second inward current $(i_{si})$ was studied by the two microelectrode voltage clamp technique in the sino-atrial node of the rabbit. The slow component $(i_{si,2})$ of the second inward current was sometimes identified and $i_{si}$ behaved as if it were a mixture of two currents. We analysed the $(i_{si,2})$ in relation to membrane potential and frequency of voltage clamp pulses. 1) Membrane was held at -40mV which was usually found to be zero current level. When depolarizing pulses were applied, the slow inward current $(i_{si})$ was activated. 2) It was shown that there are three categories of the $i_{si}$ activation by the low level of depolarizing clamp pulses. Moderately fast inward current with single component was developed in most cases in the presence of tetrodotoxin(TTX). But sometimes there was two separate components of $i_{si}$ activation in the peak level and the time course. Thirdly the only slow component of $i_{si}$ was found in rare cases. 3) The activation of $(i_{si,2})$ was dependent upon membrane potential. The $i_{si}$ shows two separate peaks during clamp depolarizations and higher clamp pulses lead to fusion of the peaks. 4) The $i_{si,2}$ activation showed that it decreased with repetitive clamp pulses and it was more evident in higher frequencies(2Hz)(negative staircase).

• Advances in Traditional Medicine
• /
• 제4권3호
• /
• pp.157-161
• /
• 2004

We showed the effects of the traditional herbal medicine, Jukyeoondam-tang (JO-T, Zhu-ru-Wen-Dan-Tang in Chinese), on ventricular arrhythmia induced by aconitine. Electrophysiological experiments with conventional microelectrode techniques revealed that JO-T potently suppressed the aconitine-induced arrhythmias in ventricular strips of the rat. In the aconitine-induced arrhythmia model of the rat, pretreatment with JO-T $(100\;{\mu}g/ml)$ completely occluded the appearance of ventricular tachyarrhythmia (VT) or ventricular fibrillation (VF) induced by aconitine. Furthermore, the aconitine-induced ventricular arrhythmia was occluded by $Na^+$ channel blocker quinidine but was not occluded by $K^+$ channel blocker glibenclamide $(3\;{\mu}mol/L)\;and\;Ca^{2+}$ channel blocker nifedipine $(10\;{\mu}mol/L)$. We also confirmed the effect of JO-T in the ischemia-reperfusion (I/R)-induced arrhythmia model of the rat. JO-T did not affect the I/R-induced arrhythmias in rats. JO-T may alleviate the risk of ventricular arrhythmias following aconitine. These results suggest that JO-T is a potent antiarrhythmic drug having a$Na^+$ channel-blocking action.

• 한국응용약물학회:학술대회논문집
• /
• 한국응용약물학회 2003년도 Annual Meeting of KSAP : International Symposium on Pharmaceutical and Biomedical Sciences on Obesity
• /
• pp.112-112
• /
• 2003

Voltage-gated $K^{+}$ (Kv) channels represent a structurally and functionally diverse group of membrane proteins. These channels play an important role in determining the length of the cardiac action potential and are the targets for antiarrhythmic drugs. Many $K^{+}$ channel genes have been cloned from human myocardium and functionally contribute to its electrical activity. One of these channels, Kv1.5, is one of the more cardiovascular-specific $K^{+}$ channel isoforms identified to date and forms the molecular basis for an ultra-rapid delayed rectifier $K^{＋}$ current found in human atrium. Thus, the blocker of hKv1.5 is expected to be an ideal antiarrhythmic drug for atrial fibrillation. Chelidonine was isolated from Chelidonium majus L. We examined the effect of chelidonine on the hKv1.5 current expressed in Ltk-cells using whole cell mode of patch clamp techniques. Chelidonine selectively inhibited the hKv1.5 current expressed in Ltk-cells in a concentration-dependent manner, whereas did not affect the HERG current expressed in HEK-293 cells. Additionally, chelidonine reduced the tail current amplitude recorded at -50 mV after 250 ms depolarizing pulses to +60 mV, and slowed the deactivation time course resulting in a 'crossover' phenomenon when the tail currents recorded under control conditions and in the presence of chelidonine were superimposed. We found that chelidonine also inhibited the $K^{+}$ current in isolated human atrial myocytes where hKv1.5 channels were predominantly expressed. Furthermore, we examined the effects of chelidonine on the action potentials in rabbit hearts using conventional microelectrode technique. Chelidonine prolonged the action potential durations (APD) of atrial, ventricular myocytes and Purkinje fibers in a dose-dependent manner. However, the effect of chelidonine on atrial APD was frequency-dependent whereas the effect of chelidonine on the APDs of ventricular myocytes and Purkinje fibers was not frequency- dependent. Also, the selective action of chelidonine on heart was more potent than dofetilide, $K^{+}$ channel blocker.

• 대한전자공학회논문지
• /
• 제17권6호
• /
• pp.58-64
• /
• 1980

최근 생휴의 신경계통에서 발생하는 징소한 전기경상의 관찰을 통하여 생휴의 신경작용을 연구하는 활동이 증대 되어가고 있다. 본논문에서는 개개의 신경세포에서 발생하는 징소전압을 측정하기 위하여 반도휴집적회로 제조기술을 이용하여 제작한 집적회로형 초미소전극배열의 제조방법과 전기적 특성에 관하여 기술하였다. 피측정극경세포의 크기와 종류에 따라 집적전극의 크기를 수μ∼수10μ 범위내에서 정확한 치수에 맞혀 제작할 수 있음을 실험적으로 확인하였다. 광학적 photolithograthy방법을 사용하여 전극의 형상을 결정하기 때문에 어떠한 형태의 전극도 만들 수 있다. 이 방법으로 만든 7소자전극위에 두께 3000A의 유리 절록층을 덮었을 때에 Rinser 용액중에서의 전극의 임피던스는 주파수 범위 10Hz∼1KHz 범위에서 약 1MΩ∼100KΩ 정도로 비교적 낮았지만 Si2N4, 절록층을 사용하면 Na+이온의 확산도 방지되고 임피이던스 특성도 보다 좋게 된다. 이 형식의 전극은 각각의 전치증폭기와 함께 단일Si? 위에 monolithic형태로 집적하여 제조할 수 있기 때문에 S/N 비와 임피이던스 특성을 훨씬 더 개선할 수 있다. 그리고 전극의 출력신호의 도출에 있어서는 multiplex 방식을 사용함으로써인출도선과 수를 감소시킬 다중신호측정도 가능하게 된다. 본방법으로 제조한 전극배열을 이용하여 실제로 생휴의 신경전위를 측정한 결과를 제시하였다.

• Journal of Korean Neurosurgical Society
• /
• 제37권2호
• /
• pp.112-115
• /
• 2005

Objective: Thalamic lesioning and deep brain stimulation(DBS) have proved to be beneficial to the treatment of essential tremor(ET). The authors compared the effects and complications of two modalities. Methods: A total of 34 patients with ET were treated with ventral intermediate(Vim) nucleus thalamotomy or Vim DBS from May 1999 to May 2003. The procedure of lesioning or stimulation were performed as usual manner with or without microelectrode recording. Postoperatively, utilizing the various combinations of frequency, voltage and pulse width optimized the stimulation. The degree of improvements of tremor and the occurrence of the complications were evaluated postoperatively and at follow-up. Results: There were 38 procedures, including 27 with Vim thalamotomy and 11 with DBS, in 34 patients. Of the thalamotomy group, left Vim lesioning is 25 and right one is 2. Follow-up duration ranged from 12 to 57 months. In the thalamotomy group, the rate of overall good outcome was 88.9% but 12 patients (44.4%) showed permanent adverse effects. In the cases of stimulation, the rate of overall good outcome was 90.9% and two patients had acceptable dysarthria. Conclusion: Both Vim thalamotomy and Vim DBS were effective for the treatment of ET, although perioperative adverse effects tended to be higher in patients who had thalamotomy. In cases of DBS, adjustments of stimulation parameters enabled an acceptable position to be achieved with tremor control and unwanted effects.

• Journal of Korean Neurosurgical Society
• /
• 제46권4호
• /
• pp.346-350
• /
• 2009

Objective : The purpose of this study was to analyze in detail the relationship between outcome and time course of effect in medically refractory primary cervical dystonia (CD) with phasic type that was treated by bilateral globus pallidus internus (Gpi) deep brain stimulation (DBS). Methods : Six patients underwent bilateral implantation of DBS into the Gpi under the guide of microelectrode recording and were followed for $18.7{\pm}11.1$ months. The mean duration of the CD was $5.8{\pm}3.4$ years. The mean age at time of surgery was $54.2{\pm}10.2$ years. Patients were evaluated with the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) and relief scale using patient self-reporting. Results : The TWSTRS total scores improved by 64.5%, 65.5%, 75.8%, and 76.0% at 3, 6, 12 months, and at the last available follow-up after surgery, respectively. Statistically significant improvements in the TWSTRS scores were observed 3 months after surgery (p=0.028) with gradual improvement up to 12 months after surgery, thereafter, the improvement was sustained. However, there was no statistically significant difference between the scores at 3 and 12 months. Subjective improvement reported averaged $81.7{\pm}6.8%$ at last follow-up. Mild dysarthria, the most frequent adverse event, occurred in 3 patients. Conclusions : Our results show that the bilateral Gpi-DBS can offer a significant therapeutic effect from 3 months postoperatively in patients with primary CD with phasic type, without significant side effects.

• The Korean Journal of Physiology
• /
• 제16권2호
• /
• pp.119-128
• /
• 1982

The frog truncus arterious were studied with conventional glass microelectrode technique in order to elucidate the underlying mechanism of spontaneous pacemaker activity. The analyses were focussed on the ionic nature of pacemaker current by changing the concentrations of extracellular $K^+$ and, $Na^+$, or by using blockers of K- and Ca-current and chronotropic transmitters. 1) The action potential of the spontaneously active truncus arteriosus has some characteristic feature of maximal distolic potential ranged from -65 to -75 mV, resting potential from -45 to -50 mV and overshoot voltage about +30 mV, respectively. Duration of the action potential taken from rapid upstroke to maximal diastolic potential was about 600 msec. Usual discharge rate was $25{\sim}30/min$ at room temperature $(18{\sim}20^{\circ}C)$. 2) The sensitivity of the resting membrane potential to change extracellular potassium concentrations $(0{\sim}12\;mM)$ was relatively low. Transient hyperpolarization was appeared in the 12 mM K Ringer after 10 min exposure to 0 mM K and it could be related to Na-pump reactivation by high potassium. 3) Reduction of extracellular sodium concetrations diminished the amplitude and frequency of the action potential. In Ringer solution containing 30% Na (substituted by equimolar Tris), spontaneous activity stopped but reappeared as very slow and small action potential. There was no spotaneous activity in zero Na Ringer solution. 4) Caesium(10 mM), K-current blocker decreased the frequency of the action potential and also pacemaker depolarization. Manganese (2 mM) known to be Ca-current antagonist, blocked spontaneous activity completely. 5) Adrenaline and acetylcholine had no chronotropic effect. But adrenaline increased the duration of plateau phase and the magnitude of the action potential in the follower cell. It is concluded that K-, Na-and Ca-current components are involved in the genesis of spontaneous activity of the frog truncus arteriosus like cardiac pacemaker tissues. But the insensitivity of truncus arteriosus to adrenaline and acetylcholine indicates that there are some different control mechanisms of spontaneous rhythm in two tissues.

• 대한수의학회지
• /
• 제40권4호
• /
• pp.691-699
• /
• 2000

We investigated the effects of nitric oxide (NO) donors, S-nitroso-L-cysteine (Cys-NO) and 3-morpholinosydnonimine hydrochloride (SIN-1), on the contractile and electrical activity of the circular muscle of guinea pig gastric antrum by using intracellular microelectrode technique. The gastric antral circular muscle showed spontaneous phasic contraction and slow wave of membrane potential. Cys-NO ($0.001{\sim}10{\mu}M$) and SIN-1 ($0.001{\sim}100{\mu}M$) reduced not only the tonic and phasic contraction but also the amplitude of slow wave in a concentration dependent manner. NO donors were more potent to inhibit phasic contraction than to do slow wave. These inhibitory effects of NO donors were mimicked by the membrane permeable guanosine-3',5'-cyclic monophosphate (cGMP) analogue, 8-bromo-cyclic GMP (8-br-cGMP, $10{\sim}300{\mu}M$). The inhibitory effects of SIN-1 and Cys-NO were antagonized by the guanylate cyclase inhibitor, 1H[ [1,2,4]oxadiazolo[4,3,-a]quinoxalin-1-one (ODQ, $10{\mu}M$). These results suggest that the inhibitory effects of NO donors on the mechanical and electrical activity is mainly mediated by cGMP pathway.