CALCIUM MODULATION OF THE SPONTANEOUS ACTIVITY AND THE IONIC CURRENTS IN RABBIT ATRIO-VENTRICULAR NODAL CELLS

Modulation by changing the extracellular Ca²⁺ concentration ([Ca]ₒ) of the electrophysiological activity in isolated rabbit atrio-ventricular (AV) nodal cells was investigated using the two-microelectrode voltage-clamp technique. Low [Ca]ₒ (0.9 mM or Ca²⁺-free) decreased the rate of spontaneous beating, but the maximum rate of depolarization was significantly enhanced. Simultaneously, the [Ca]ₒ decline tended to increase the action potential amplitude, prolong the action potential duration (at 50% repolarization), and shorten the cycle length. The maximum diastolic potential was hyperpolarized. But these factors were not significant. In contrast, elevation of [Ca]ₒ to 5.4 or 10 mM (from 1.8 mM) transiently stimulated, but then inhibited the spontaneous activity. The effects on the action potential parameters were rather depressant. In voltage-clamp experiments, the [Ca]ₒ elevation increased the maximum onductances for the slow inward current and the delayed outward K⁺ current, whereas the [Ca]ₒ decline decreased them. An arrhythmia occurred in 4 out of 6 preparations only at 10 mM [Ca]ₒ. These results indicate that [Ca]ₒ would modulate the electrical activity of the AV nodal cells due to conductance changes in the ionic channels, but high [Ca]ₒ induces rather the depressant effects

CARDIOPROTECTIVE ACTION OF AMILORIDE, A POTASSIUM SPARING DIURETIC DRUG, IN CANINE VENTRICULAR MUSCLE

Electrophysiological and mechanical effects and alteration of intracellular Ca²⁺ concentration in canine ventricular muscle by amiloride, a potassium sparing diuretic drug, were examined, using conventional microelectrode technique and fura-2 Ca²⁺-sensitive fluorescent dye. Amiloride (50 μM) depressed the action potential amplitude by 8.2±1.4% (n=8, P<0.05) and the maximum rate of depolarization by 16.2±2.0% (n=8, P<0.01). In addition, the action potential duration was prolonged by 26.7±3.4% (n=6, P<0.05) at 30 μM, and the resting potential was depolarized by 11.8±1.7% (n=6, P<0.05) at 0.5 mM amiloride. In contrast, amiloride (0.5 to 1 mM) significantly increased the contractile force by 8 to 30% (n=8), but tended to decrease it at lower concentrations (30 μM to 0.1 mM). The positive inotropic effect was not affected by propranolol (0.1 μM), a β-adrenoceptor blocker. In fura-2 loaded ventricular myocytes, amiloride (1 mM) initially elevated cellular Ca²⁺ level ([Ca]₁) by 24.5±2.9% (n=6, P<0.01), and during the application, the [Ca]₁ level declined. These results indicate that amiloride possesses complex cardiac (protective) actions : electrical inhibitory and mechanical stimulatory actions, accompanied with the elevation of cellular Ca²⁺ concentration

PROTON MODULATIONS ON THE IONIC CURRENTS IN RABBIT ATRIO-VENTRICULAR NODAL CELLS

Modulations of changing the extracellular pH on the electrophysiological activity of isolated rabbit atrio-ventricular (AV) nodal cells were investigated using the two microelectrode voltage-clamp technique. Increasing pH from 7.4 to 9.5 enhanced spontaneous activity. The action potential amplitude and the maximum rate of depolarization were decreased. The action potential duration at 50% repolarization and the cycle length were shortened. The maximum diastolic potential was hyperpolarized. The pH elevation increased the maximum conductances for both the slow inward current and the delayed outward current systems. In contrast, a decline of pH from 7.4 to 5.5 inhibited the activity and the ionic currents. The effects on the action potential parameters were reversed. However, both acidification and alkalinization failed to affect the gating kinetics of the channels. These results suggest that H⁺ would modulate the electrical activity of the AV nodal cells, due not to an alteration of the membrane surface charge, but to a direct protonation of the ionic channels

難治性の良性発作性頭位めまい症はヘッドアップした姿勢で就寝することにより治り得る：6ヶ月間のランダム化比較試験

Objectives: The aim of the present study was to assess head-position management for intractable idiopathic benign paroxysmal positional vertigo (BPPV) when lying down. We hypothesized that head-up sleep (HUS) could prevent free-floating otoliths from entering the semicircular canals. Study design: A prospective two-arm multicenter randomized controlled trial. Methods: BPPV was diagnosed in 611 patients (611/1,520; 40.2%) according to the 2015 diagnostic guidelines issued by the International Classification of Vestibular Disorders. Among them, 201 patients were intractable (201/611; 32.9%), 88 of whom were idiopathic and subsequently enrolled in the study. Patients randomly received intervention with HUS at greater than 45° (n = 44) or head-down sleep (HDS; n = 44) when lying down. Before treatment, they completed several examinations, including subjective visual vertical (SVV). The specific diagnoses for the 88 patients with BPPV included horizontal type cupula (n = 40), horizontal type canal (n = 13), posterior type (n = 26), and probable and/or atypical BPPV (n = 9). Results: Patient backgrounds did not differ significantly between the HUS and HDS groups. Visual analog scale (VAS) scores of vertiginous sensation were significantly lower in the HUS group than in the HDS group at both the third month and sixth month post-treatment. Positional/positioning nystagmus observed just before treatment disappeared significantly more often in the HUS group than in the HDS group until the sixth post-treatment month. Further, especially in HUS group, VAS scores in SVV- group (n = 24) were significantly lower than those in the SVV+ group (n = 20) sixth month post-treatment. Conclusions: Controlling free-floating otoliths is not easy due to aging of the otolith organs. Repeatedly returning the endless free-floating debris from the canals to the utricle through physical means is not a good strategy. Therefore, HUS when lying down at home could be recommended as an initial treatment for patients with intractable idiopathic BPPV. Level of evidence: 1b.博士（医学）・甲第764号・令和3年3月15日© 2019 The Authors. Laryngoscope Investigative Otolaryngology published by Wiley Periodicals, Inc. on behalf of The Triological Society. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made