Potassium current kinetics in Myxicola axons. Effects of conditioning prepulses.

In Myxicola giant axons the time constants for activation of the potassium conductance (GK) after prepulses less depolarized than a test pulse are comparable to the time constants for turn off of GK after prepulses more depolarized than the same test pulse. The absolute magnitude of the steady-state level of GK is also independent of prepulse amplitude in Myxicola. The results are contrasted with recent observations on voltage-clamped frog nodes.

Disruption of the perineurium in amphibian peripheral nerve: morphology and physiology.

Removal of a small piece of perineurium in amphibian nerve causes a lesion consistent with the presence of extensive demyelination. Conduction velocity is reduced by 30 to 40%, and most of the fibers that still conduct are labile, with abnormally low blocking temperatures and unusual susceptibility to conduction block induced by changes in extracellular electrolytes. Application of drugs that inhibit the delayed K+ conductance restores conduction to fibers blocked by temperature elevation and ionic changes. This preparation may prove useful in studies of the pathophysiology of demyelinating diseases.

Hippocampal CA1 neuronal properties in genetically epilepsy-prone rats: evidence for increased excitation.

The genetically epilepsy prone rats (GEPRs) are abnormally susceptible to seizures with a variety of treatments and can be used as a model to study generalized seizure predisposition involving the brainstem and forebrain structures. We investigated the basic membrane and synaptic properties of hippocampal CA1 cells in Sprague-Dawley (SD) rats and GEPRs. Several differences in cellular properties were observed in the GEPRs. These include an increase in membrane input resistance and reduced spike frequency adaptation in the majority of GEPR cells. A decrease in the amount of current required to elicit a 5-mV EPSP was observed in the GEPR. A marked increase in excitability with paired pulse stimulation was also observed in GEPRs both in extracellular population spikes and intracellular EPSPs. Applying bicuculline, a GABAA antagonist, markedly increased paired pulse facilitation of the population spike in SD rats but in GEPRs produced only a minimal effect on facilitation. This difference suggests reduced GABAA-mediated inhibition in GEPR hippocampus with paired pulse stimulation. Several factors could interact or act independently to produce these effects because the epileptic phenotype in GEPRs is regulated by multiple genes.

Evidence for decreased calcium dependent potassium conductance in hippocampal CA3 neurons of genetically epilepsy-prone rats.

The genetically epilepsy-prone rat (GEPR) has become an important model to study genetic predisposition to epilepsy involving not only the brainstem but also forebrain structures. Previous work in CA1 hippocampal cells showed a reduction in spike frequency adaptation and only subtle changes in slow afterhyperpolarization (AHP). As important differences exist in calcium dependent potentials in the CA1 and CA3 hippocampal cells, we compared the membrane properties of hippocampal CA3 cells in GEPRs and Sprague-Dawley (SD) rats. There was no significant difference in the resting membrane potential, input resistance, charging time constant or rheobase between GEPRs and SD rat neurons. The action potential amplitude and the width at half maximal amplitude did not differ. A marked reduction in spike frequency adaptation accompanied by a very significant reduction in AHP was seen in the GEPR rats. Since calcium dependent potassium conductance produces both spike frequency adaptation and AHP, our results suggest that this conductance is reduced in the GEPR CA3 neurons.

Delayed brain abscess related to a retained foreign body with culture of Clostridium bifermentans. Case report.

Although it is well documented that retained foreign bodies are associated with delayed intracranial abscess, there are few reports of anaerobic organism growth. A case is presented in which a left parieto-occipital abscess surrounded a metallic fragment implanted when a mortar shell exploded in Vietnam 15 years before. The diagnostic evaluation and surgical management of this case are presented.

Characteristics of sodium tail currents in Myxicola axons. Comparison with membrane asymmetry currents.

Sodium currents after repolarization to more negative potentials after initial activation were digitally recorded in voltage-clamped Myxicola axons compensated for series resistance. The results are inconsistent with a Hodgkin-Huxley-type kinetic scheme. At potentials more negative than -50 mV, the Na+ tails show two distinct time constants, while at more positive potentials only a single exponential process can be resolved. The time-course of the tail currents was totally unaffected when tetrodotoxin (TTX) was added to reduce gNa to low values, demonstrating the absence of any artifact dependent on membrane current. Tail currents were altered by [Ca++] in a manner consistent with a simple alteration in surface potential. Asymmetry current "off" responses are well described by a single exponential. The time constant for this response averaged 2.3 times larger than that for the rapid component of the Na+ repolarization current and was not sensitive to pulse amplitude or duration, although it did vary with holding potential. Other asymmetry current observations confirm previous reports on Myxicola.

The effect of haloperidol on the ionic currents in the voltage-clamped node of Ranvier.

Haloperidol (Haldol) selectively inhibits sodium currents at the voltage-clamped node of Ranvier at concentrations ranging from 0.013 to 13 muM. The action potential is reduced or abolished while the membrane potential is not significantly changed. The dose-response curve is described by a Langmuir adsorption isotherm with an apparent dissociation constant of 6 X 10(-7) M. Sodium current time-to-peak and the permeability-voltage relationship are not affected, although at higher concentrations the inactivation time constant is slightly increased. Potassium currents are not altered except at 13 muM where there is an occasional nonsystematic effect. Leakage currents are not changed at any concentration.

Activation-inactivation coupling in Myxicola giant axons injected with tetraethylammonium.

Myxicola giant axons internally injected with tetraethylammonium chloride to block potassium currents were examined under voltage clamp. The sodium inactivation time constants obtained from the decline in INa during step depolarizations were substantially smaller than those obtained using conditioning prepulses to the same potentials and the ratios agreed with previous observations using TTX. Inactivation shifts were also measured and found to be comparable to previous results.

Slow sodium inactivation in Myxicola axons. Evidence for a second inactive state.

Sodium inactivation and reactivation have been examined in voltage-clamped Myxicola axons after long-lasting membrane depolarizations produced either directly by changes in holding potential or indirectly by elevation of external K+ concentration. The results suggest the existence of a second inactivated state of the sodium channel with associated voltage-dependent rate constants at least two orders of magnitude lower than those of the fast inactivation process commonly examined. No specific influence of external [K+] on slow Na+ inactivation could be detected.

Chronic vagus nerve stimulation increases the latency of the thalamocortical somatosensory evoked potential.

The Neurocybernetic Prosthesis (NCP) is a pacemaker-like device that has been designed to provide chronic intermittent vagus nerve stimulation. It is currently under study for the treatment of refractory partial onset epilepsy, and preliminary studies have indicated that partial onset seizures are improved by this therapy. The mechanisms by which it exerts its antiepileptic effect are not well understood. Although there are extensive pathways to the forebrain from the nuclei of the vagus nerve, the evidence that the NCP alters neural transmission outside the vagal system is limited. We prospectively examined somatosensory and brain stem auditory evoked potentials (BAEPs) in three patients receiving NCP implantation to determine if changes in these studies occur as a result of chronic vagus nerve stimulation. The results demonstrate a significant prolongation of the cervicomedullary to thalamocortical potential (N13-N20) interval on somatosensory evoked potential (SSEP) studies following activation of the device. No other significant changes were seen on SSEP or BAEP in the NCP implanted patients or normal controls. The findings suggest that chronic vagus nerve stimulation does alter neuronal networks outside of the brain stem vagus system, and may potentially provide a means to clinically monitor and titrate this therapy.