SUMMARY1. Effect of intracellular ATP on Cl-current (I1c) mediated by the GABA (yaminobutyric acid) receptor subtype, GABAA, was studied in dissociated nucleus tractus solitarii (NTS) neurones using the whole-cell mode of patch clamp. A concentration-jump technique termed 'Y tube' was used to rapidly apply agents externally. Dissociated neurones were obtained from 1-to 3-week-old rats.2. When the patch-pipette solution contained 2 mM-ATP, the amplitude of Ic elicited by 10-5 M-GABA did not show any time-dependent decrease (apparent rundown), for more than 60 min after the initial recording. In the presence of ATP, the half-maximum concentration (KD) and Hill coefficient calculated from the GABA concentration-response curve were 9-12 ,lM and 1-47, respectively.3. In the absence of intracellular ATP, the amplitude of GABA-induced Ic, decreased with time. The relative peak amplitudes after 20 and 60 min from the initial recording were 0-40 + 0-09 (n = 11) and 0 16 + 0-05 (n = 8) with respect to the initial response.4. Removal of Mg2+ from the internal solution induced run-down of the GABA response even in the presence of 2 mM-intracellular ATP, suggesting that both intracellular ATP (2 mm or more) and Mg2+ are necessary to prevent run-down of the GABA response.5. Activation of dephosphorylation processes by alkaline phosphatase 12. It was concluded that intracellular ATP may regulate the affinity of the GABAA receptor-Cl-channel complex via an intracellular ATP receptor.

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PurposeNifekalant is a pure potassium channel blocker that has been used to treat ventricular tachyarrhythmias since 1999 in Japan. Intravenous amiodarone was approved later than nifekalant in Japan, and it is still unclear which of the two agents is superior. The aim of this study was to compare the efficacy of nifekalant and amiodarone for resuscitation of out-of-hospital cardiopulmonary arrest caused by shock-resistant ventricular fibrillation.MethodsFrom December 2005 to January 2011, ambulance services transported 283 out-of-hospital cardiopulmonary arrest patients to our hospital. Of these, 25 patients were treated with nifekalant or amiodarone in response to ventricular fibrillation that was resistant to two or more shocks. We undertook a retrospective analysis of these 25 patients.ResultsWe enrolled 20 men and 5 women with a mean age (± standard deviation) of 61.1 ± 16.4 years. All 25 patients were treated with tracheal intubation and intravenous epinephrine. Fourteen patients received nifekalant and 11 patients received amiodarone. The rates of return of spontaneous circulation (ROSC) (nifekalant, 5/14, versus amiodarone, 4/11; P = 0.97) and survival to discharge (nifekalant, 4/14, versus amiodarone, 2/11; P = 0.89) were not significantly different between the two groups. The time from nifekalant or amiodarone administration to ROSC was 6.0 ± 6.6 and 20.3 ± 10.0 min, respectively, which was significantly different (P < 0.05).ConclusionIn this small sample size study, nifekalant, compared with amiodarone, is equally effective for ROSC and survival to discharge after shock-resistant ventricular fibrillation and can achieve ROSC more quickly. Further prospective studies are needed to confirm our results.

It has been reported that direct hemoperfusion with the adsorbent column using polymyxin B‐immobilized fiber (DHP with PMX‐F column) ameliorates hyperdynamic circulation in septic shock and improves survival rate. However, the clinical characteristics of patients with an improvement of septic shock after DHP with PMX‐F column have not been evaluated. To clarify this issue, the clinical profiles of 46 patients who were suggested to have gram‐negative septic shock and treated using DHP with PMX‐F column were analyzed retrospectively. Of 46 patients, 31 were diagnosed with gram‐negative septic shock (G group). Mean arterial pressure (MAP) just before DHP with PMX‐F column was not different between the G and the non‐G group. As compared with the non‐G group, the G group had a higher cardiac index (CI) and a lower systemic vascular resistance (SVR). Significant increases in MAP and SVR with a significant decrease in CI were observed after DHP with PMX‐F column in the G group. In the non‐G group, MAP was significantly increased after the DHP therapy, but systemic hemodynamics were unchanged. Patients in the G group who fulfilled the following criteria were considered as the effective group: MAP was elevated more than 10 mm Hg or 125% of the basal MAP and/or the dose of vasopressors was reduced after DHP with PMX‐F column. Twenty‐one patients (67.8%) were in the effective group. In comparison with the effective group, the noneffective group was characterized by a significant increase in CI before DHP with PMX‐F column. All patients with a CI less than 6 L/min/m2 were in the effective group. These data suggest that DHP with PMX‐F column was useful for patients with Gram‐negative septic shock who did not have severe hyperdynamic circulation.

SUMMARY1. Conventional whole-cell voltage-clamp technique was used to study the electrophysiological and pharmacological properties of voltage-dependent Na', K+ and Ca21 channels in parasympathetic neurones enzymatically dissociated from the paratracheal ganglia of rat trachea. The voltage-dependent Na+, K+ and Ca2+ currents (INa' IK and ICa) were separated by the use of ion subtraction and pharmacological treatments.2. INa was activated by a step depolarization more positive than -50 mV and fully activated at positive potentials more than + 10 mV. The inactivation phase of INa consisted offast and slow exponential components (Tif and Tis' respectively). The rif and r.i were voltage dependent and decreased with a more positive step pulse.3. The time course for recovery of INa from the complete inactivation exhibited two exponential processes.4. The reversal potential of INa was equal to the Na+ equilibrium potential (ENa) and resembled a simple Na+ electrode depending only on external Na+ concentration.5. Tetrodotoxin (TTX) reduced INa without affecting the current kinetics in a concentration-dependent manner, and the concentration of half-maximal inhibition (IC50) was 6 x 10' M. There was no TTX-resistant component of INa in any of the cells tested.6. Scorpion toxin increased the peak amplitude of INa and prolonged the inactivation phase in a time-and concentration-dependent manner. In the presence of toxin, both ris and the fractional contribution of the slow current component to total INa increased concentration dependently.7. High-threshold (L-type) ICa was activated by a step depolarization more positive than -30 mV and reached a peak at near 0 mV in the external solution with 2-5 mm Ca2+. The current was inactivated to only a small extent (< 10%) during 100 ms of depolarizing step pulse. There was no low-threshold (T-type) ICa in this preparation.8 K. AIBARA, S. EBIHARA AND KY AKAIKE 9. The inactivation process of the L-type ICa was dependent on Ca2+ influxes (ICadependent inactivation).10. Relative maximum peak currents of divalent cations passing through the Ltype Ca2+ channels were in the order of IBa > ICa > ISr.11. Organic and inorganic Ca2+ antagonists blocked the ICa in a concentrationdependent manner. The order of inhibition was wo-conotoxin > flunarizine > nimodipine > D600 > diltiazem > amiloride for organic blockers and La3+ > Cd2+ > Ni2+ > Co2+ for inorganic ones.12. Three types of IK were observed; i.e. an inwardly rectifying current, a delayed outward current ('KD) and a transient outward current ('A) 13. Depolarizing pulses from a holding potential (VH) of -90 mV elicited K+ currents which seemed to suggest the existence of two distinct cell types. The 'A was observed in the majority of cells (44 out of 63 cells). The IKD was elicited in all cells tested.14. 'KD was activated by step pulses more positive than -20 mV, slowly inactivated (T > 1 s) and reduced by adding tetraethylammonium (IC50 was 4 4 mM).15. The IA was characterized by a rapid activation and inactivation. The amplitude o...