Youji Takeda

Effects of MS-551, a new class III antiarrhythmic drug, on action potential and membrane currents in rabbit ventricular myocytes.

1 Electrophysiological effects of MS‐551, a new class III antiarrhythmic drug, were examined and compared with those of (+)‐sotalol in rabbit ventricular cells. 2 In rabbit ventricular muscles stimulated at 1.0 Hz, MS‐551 (0.1–10 μm) and (+)‐sotalol (3–100 μm) prolonged action potential duration (APD) and effective refractory period without affecting the maximum upstroke velocity of phase 0 depolarization . The class III effect of MS‐551 was approximately 30 times more potent than that of (+)‐sotalol. 3 Class III effects of MS‐551 and (+)‐sotalol showed reverse use‐dependence, i.e., a greater prolongation of APD at a longer cycle length. 4 In rabbit isolated ventricular cells, 3 μm MS‐551 and 100 μm sotalol inhibited the delayed rectifier potassium current (IK) which was activated at more positive potentials than −50 mV and saturated around + 20 mV. 5 MS‐551 at a higher concentration of 10 μm decreased the transient outward current (Ito) and the inward rectifier potassium current (IK1) although 100 μm sotalol failed to inhibit these currents. 6 MS‐551 is a non‐specific class III drug which can inhibit three voltage‐gated K+ channels in rabbit ventricular cells.

Cyclic GMP-mediated inhibition of L-type Ca2+ channel activity by human natriuretic peptide in rabbit heart cells.

1 Effects of atrial natriuretic peptide (ANP) on the L‐type Ca2+ channels were examined in rabbit isolated ventricular cells by use of whole‐cell and cell‐attached configurations of the patch clamp methods. ANP produced a concentration‐dependent decrease (10–100 nm) in amplitude of a basal Ca2+ channel current. 2 The inactive ANP (methionine‐oxidized ANP, 30 nm) failed to decrease the current. 3 8‐Bromo‐cyclic GMP (300 μm), a potent activator of cyclic GMP‐dependent protein kinase (PKG), produced the same effects on the basal Ca2+ channel current as those produced by ANP. The cyclic GMP‐induced inhibition of the Ca2+ channel current was still evoked in the presence of 1‐isobutyl‐3‐methyl‐xanthine, an inhibitor of phosphodiesterase. ANP failed to produce inhibition of the Ca2+ channel current in the presence of 8‐bromo‐cyclic GMP. 4 In the single channel recording, ANP and 8‐bromo‐cyclic GMP also inhibited the activities of the L‐type Ca2+ channels. Both agents decreased the open probability (NP0) without affecting the unit amplitude. 5 The present results suggest that ANP inhibits the cardiac L‐type Ca2+ channel activity through the intracellular production of cyclic GMP and then activation of PKG.

Effects of ATP‐sensitive K+ channel blockers on the action potential shortening in hypoxic and ischaemic myocardium

1 In order to determine whether activation of adenosine triphosphate (ATP)‐sensitive K+ channels exclusively explains the hypoxia‐ and ischaemia‐induced action potential shortening, effects of tolbutamide and glibenclamide on changes in action potential duration (APD) during hypoxia, metabolic blockade or experimental ischaemia were examined in guinea‐pig and canine isolated myocardium by standard microelectrode techniques. 2 With use of patch clamp techniques, activity of ATP‐sensitive K+ channels was recorded from open cell‐attached patches of guinea‐pig isolated ventricular myocytes. The probability of opening of the K+ channels was decreased by 2 mm tolbutamide and 20 μm glibenclamide to almost the same extent, whereas it was increased by 100 μm pinacidil. 3 In guinea‐pig papillary muscles a marked shortening of the action potential produced by 100 μm pinacidil was completely antagonized by 2 mm tolbutamide or 20 μm glibenclamide. 4 In guinea‐pig papillary muscles exposed to hypoxic, glucose‐free solution or dinitrophenol (10 μm)‐containing, glucose‐free solution, APD declined gradually and twitch tension decreased. Pretreatment with glibenclamide partially but significantly inhibited the action potential shortening, whereas tolbutamide failed to improve it during hypoxia or metabolic blockade. 5 When in canine isolated myocardium, experimental ischaemia was produced by the cessation of coronary perfusion, APD was gradually shortened. The action potential shortening was partially but not completely inhibited by pretreatment with 20 μm glibenclamide. 6 These results suggest that changes in membrane current(s) other than the outward current through ATP‐sensitive K+ channels also contribute to the action potential shortening in hypoxic or ischaemic myocardium.

Mechanism of the membrane depolarization induced by oxidative stress in guinea-pig ventricular cells.

Mechanism of the membrane depolarization induced by oxidative stress was examined using ion-selective microelectrode and patch clamp techniques. In guinea-pig papillary muscles stimulated at 0.5 Hz, cumene hydroperoxide (CH) at a concentration of 300 microM decreased the resting membrane potential and shortened the action potential, concomitantly with muscle contracture. The membrane depolarization was not associated with a significant decrease in intracellular potassium ion activity, indicating that the depolarization is not due to a decrease in potassium equilibrium potential resulting from leak of intracellular K+. In isolated guinea-pig ventricular cells. CH (10-30 microM) consistently decreased the inward rectifier potassium current and slightly decreased the calcium current. In cell-attached patches CH inhibited the opening of the inward rectifier K+ channel without affecting the unit amplitude of the single channel current. Thus, the depolarization of the resting membrane induced by oxidative stress is, at least in part, due to the inhibition of the inward rectifier K+ channel activity, and may play an important role in the genesis of reperfusion-induced arrhythmias.

Acute Psychosis During Intracranial EEG Monitoring: Close Relationship Between Psychotic Symptoms and Discharges in Amygdala

Summary:  Purpose: This report examined the underlying mechanism of psychosis associated with epilepsy.

Generalized spike-wave discharges involve a default mode network in patients with juvenile absence epilepsy: A MEG study

This study uses magnetoencephalography (MEG) to examine whether cortical regions that constitute a default mode network are involved during generalized spike-wave discharges (GSWs) in patients with juvenile absence epilepsy (JAE). We studied five JAE patients for whom MEG was recorded using a 204-channel, whole-head gradiometer system. Dynamic statistical parametric mapping (dSPM) was done to estimate the cortical source distribution of GSW. The dSPM results showed strong medial prefrontal activation in all patients, with activation in the posterior cingulate and precuneus in three of five patients simultaneously or slightly after medial prefrontal activation. Furthermore, dSPM showed that the initial activation of a GSW appears in the focal cortical regions. Cortical regions that constitute a default mode network are strongly involved in the GSW process in some patients with JAE. Results also show that focal cortical activation appears at the onset of a GSW.

Clinical factors associated with post-ictal headache in patients with epilepsy

Objectives– To determine the incidence of post‐ictal headaches (PIH) and clinical risk factors associated with the occurrence of PIH in patients with localization‐related epilepsy. Materials and methods– The subjects were 77 patients with temporal lobe epilepsy (TLE), 34 patients with occipital lobe epilepsy (OLE), and 50 patients with frontal lobe epilepsy (FLE). The subjects were directly asked whether headaches occurred just after seizures. Medical charts were reviewed to ascertain the clinical characteristics of epilepsy in these patients. Results– The incidence of PIH was 23% for TLE, 62% for OLE, and 42% for FLE. The risk of PIH was significantly higher for OLE than for TLE or FLE, and for patients with generalized tonic–clonic seizures. Younger age at onset of epilepsy was also a risk factor for PIH. Conclusion– The occurrence of PIH may be related to the region of epileptic focus and the region of spread of epileptic discharges.

Magnetoencephalographic analysis of secondary bilateral synchrony.

To assess the clinical value of magnetoencephalography (MEG) in investigating the origin of secondary bilateral synchrony (SBS) in patients with partial epilepsy. MEG and simultaneous electroencephalography (EEG) were recorded with a 204‐channel whole‐head MEG system in 2 patients. The equivalent current dipoles (ECDs) for epileptic discharges on MEG were calculated according to a single dipole model. In patient 1, the ictal EEG showed bursts of bilateral synchronous 3‐Hz spike‐and‐slow‐wave complexes. ECDs obtained from the ictal MEG localized to the right medial frontal lobe. On the second patients MEG recordings, epileptic discharges corresponding to prolonged EEG bursts of bilateral synchronous spike‐and‐slow‐wave complexes were obtained. ECDs calculated from the prolonged bursts were clustered in the left medial frontal lobe. MEG detected the sources of SBS in the medial frontal lobe. MEG is extremely useful for the identification of the source of SBS.

Symptomatic generalized epilepsy associated with an inverted duplication of chromosome 15

An inverted duplication of chromosome 15 (inv dup[15] chromosome) is the most common supernumerary marker chromosome in humans. Inv dup(15) chromosomes are commonly associated with mental retardation, epilepsy, behavioral problems and structural malformations. Though epilepsies associated with inv dup(15) chromosomes are often intractable, there have been very few reports regarding the seizure manifestations or types. We report a patient with severe mental retardation and intractable epilepsy, associated with an inv dup(15) chromosome. The seizures recorded with EEG-VTR monitoring were axial and generalized tonic seizures, and our case was diagnosed as symptomatic generalized epilepsy. Molecular and cytogenetic analysis showed an inv dup(15) chromosome containing the Prader-Willi syndrome/Angelman syndrome region mapped within bands 15q 11-q13.

Persistent déjà vu associated with hyperperfusion in the entorhinal cortex

Déjà vu is a common experience among the normal population. However, in individuals with temporal lobe epilepsy, it often occurs as a seizure manifestation. The specific cause of such déjà vu is not yet known. Here, we report a case of epilepsy with persistent déjà vu. The patient described the state as if he were living the same life he had lived before. Blood perfusion single-photon-emission computed tomography (SPECT) performed during the persistent déjà vu showed hyperperfusion in the left medial temporal area; discontinuation of déjà vu was accompanied by disappearance of the hyperperfused area on SPECT. Analysis with three-dimensional co-registration of SPECT and MRI revealed that the hyperperfused area during the persistent déjà vu was in the entorhinal cortex of the left temporal lobe. According to recent theories of recognition memory, malfunction of the parahippocampal area may cause déjà vu. It is also suggested that epileptic activity in the parahippocampal area, especially the entorhinal cortex, may elicit déjà vu.