No abstract

The results in isolated myocytes indicate that KATP channels open sufficiently rapidly after starting anoxia and generate sufficiently large conductance at maintained anoxia to explain both the time course and magnitude of the ischemic K+ accumulation if an appropriate counter-ion flux is available.

Fully allogeneic, chimeric mice were established by adult thymectomy of (A x B) F1 animals, grafting parental A-type thymus under the kidney capsula, followed by lethal (900 rd) irradiation and reconstitution with B parental-type bone marrow cells treated with xenogeneic anti-T cell antiserum plus complement. Following in vivo sensitization with inactivated Sendai virus (SV) suspensions, no virus-specific T cells could be detected within the spleen cells of the mice. Upon stimulation with third-party allogenic cells in a primary mixed lymphocyte culture, spleen cells of all animals generated alloreactive cytotoxic T lymphocytes (CLT). More interestingly, upon secondary in vitro stimulation with inactivated SV-conjugated B-type stimulator cells, B-type-restricted, virus-specific CTL were inducible in each case. Upon restimulation with SV-conjugated A-type stimulator cells, A being the H-2 type of the grafted thymus, T cells of some but no all mice generated A-type-restricted, virus-specific CTL. The data suggest that in allogeneic, chimeric mice virus-specific CTL can be induced. Moreover, virus-specific CTL, restricted to the H-2 type of the lymphoid stem cell inoculum, are more readily inducible than those restricted to the H-2 type of the allogeneic thymus.

1. Mouse ventricular myocytes develop a large transient K+ outward current (ITO) which accelerates repolarization and is a crucial determinant for the regulation of the action potential duration at various heart rates. The effect of 3-hydroxybutyrate on ITO was investigated under voltage-and current-clamp conditions. 2. The drug blocked ITO in a stereoselective manner with the L-enantiomer being the effective and the D-enantiomer, the ineffective form. The blocking action of the L-enantiomer was established immediately and it could be completely washed out within several tens of seconds.3. The dose-response characteristic for the peak ITO showed a strict 1: 1 binding of the drug to the receptor with a concentration of half-maximum effect of 2 1 mmol F'.4. The action of L-hydroxybutyrate was voltage independent, did not need channel opening and preferentially affected the slow component of both inactivation and recovery from inactivation. 5. At the high concentration of 20 mmol F1 the optically inactive form, the racemate, did not affect ITO, indicating that the ineffective D-enantiomer interacts with the channels at much lower concentrations.6. At a concentration of 10 mmol F', L-hydroxybutyrate prolonged the action potential by 218 + 26 and 127 + 10% (means + S.E.M.) at 50 and 90% repolarization, respectively. 7. It is concluded that the non-physiological L-hydroxybutyrate is a novel type of blocker of ITO It interacts either with the channel itself, or with a receptor protein closely related to the channel and preferentially affects slow inactivation.

In ventricular myocardial cells of the guinea pig and the mouse, anoxia caused after a mean latency of 439 _+ 141 s and 129 _+ 23 s (mean _ S.E.M.), respectively, a large current through KgTp-channels. This current disappeared within several seconds when reoxygenating the cells but decayed also completely at maintained anoxia. The kinetics of the latter process, however, were much slower and obeyed an approximately monoexponential time course with time constants in the range of 30 s. The results suggest that in the ischaemic myocardium KATp-channels contribute only to the initial phase of extracellular K + accumulation.