Long-term modifiability of anomalous and delayed rectification in guinea pig inferior olivary neurons.
Delayed and anomalous rectification was studied in inferior olivary (I.O.) neurons in guinea pig brain stem slices maintained in vitro. Hyperpolarization of the I.O. cell beyond rest membrane potential was accompanied by anomalous rectification (AR). This consisted of 2 parts: an instantaneous and a time-dependent component. The "instantaneous" component was blocked by bath addition of Ba2+ or Cs+ and demonstrated inactivation following prolonged hyperpolarization. The time-dependent component, referred to as the gK(ol), was blocked by harmaline in concentrations of 0.1 mg/ml or by substitution of Co2+, Cd2+, or Mn2+ for Ca2+ in the bath. The gK(ol) was blocked by extracellular Cs+ but not by Ba2+. Delayed rectification (DR), consisting of 2 distinct components, was observed after membrane depolarization by more than 10 mV with respect to rest (usually at -65 mV). One of the components of the DR was found to be quite similar to the classical gK. It did not demonstrate significant inactivation with membrane potential change and was reduced by Ba2+ or tetraethylammonium (TEA). A second component of the DR demonstrated voltage-dependent inactivation and was thus referred to as gK(inact). This inactivation determined by current-clamp measurements had a sigmoidal time course, with approximately a 1 sec onset latency and a half-time to peak of 7 sec. The inactivation of gK(inact) outlasted current injection for tens of seconds to several minutes, depending on the duration and amplitude of the preceding depolarization. During this period, I.O. neurons could be easily activated and demonstrated full dendritic spikes following current injection or excitatory synaptic input that had previously been subthreshold for spike initiation. The inactivation component of the DR was removed by prolonged membrane hyperpolarization beyond rest. gK(inact) was blocked by 4-aminopyridine (4-AP; 100 microM) but not by Ba2+. This inactivation was dependent on the presence of extracellular Ca2+ or Ba2+. Addition of Co2+ or Cd2+ to the bath did not block gK(inact) but did prevent its inactivation. The modulatory effects of these different membrane conductances on the integrative properties of I.O. neurons are described. The long duration of the inactivation of DR and AR is considered as the basis for a dynamic long-term modulation of the electroresponsive and integrated properties of I.O. neurons.
D015761:4-Aminopyridine; D000631:Aminopyridines / Q000494:pharmacology; D000818:Animals; D002412:Cations / Q000494:pharmacology; D004553:Electric Conductivity; D006168:Guinea Pigs; D006246:Harmaline / Q000494:pharmacology; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000502:physiology*; D009847:Olivary Nucleus / Q000187:drug effects / Q000502:physiology*; D011188:Potassium / Q000502:physiology; D013779:Tetrodotoxin / Q000494:pharmacology
D000631:Aminopyridines; D002412:Cations; D013779:Tetrodotoxin; D015761:4-Aminopyridine; D006246:Harmaline; D011188:Potassium