Changes in excitability induced by herpes simplex viruses in rat dorsal root ganglion neurons.
The physiological properties of rat sensory neurons infected with herpes simplex type 1 viruses and maintained in cell culture were studied using intracellular recording techniques. Two syncytial (cell fusing) and two nonsyncytial strains of virus were examined; individual strains of virus had different effects on neuronal excitability. The nonsyncytial viruses caused a loss of tetrodotoxin-sensitive low-threshold action potentials and blocked hyperpolarization-activated inward rectification, but did not alter the resting membrane potential, depolarization-activated outward rectification, or render the cells leaky. These effects develop progressively over the period 5-15 hr postinfection. One syncytial strain of virus induced spontaneous electrical activity that appeared to be the result of discrete electrical coupling between sensory neuron processes; as a result, action potential discharge is synchronized in coupled neurons. A second syncytial strain of virus rendered neurons inexcitable; however, in these experiments the input resistance fell to low values, possibly as a result of extensive coupling between sensory neurons. Viral replication in sensory neurons was demonstrable with indirect immunofluorescence using an antibody to herpes simplex viruses and correlated with the onset of virally induced changes in excitability. Virally triggered changes in excitability were blocked by the specific herpes virus antimetabolite acyclovir, suggesting that viral adsorption and penetration are by themselves insufficient to evoke changes in excitability. These results suggest that herpes viruses have selective effects on the excitable mechanisms in sensory neurons that are not simply the result of a general loss of membrane conductances or the disruption of transmembrane ion gradients.
D000200:Action Potentials; D000212:Acyclovir / Q000494:pharmacology; D000818:Animals; D004553:Electric Conductivity; D004594:Electrophysiology; D005455:Fluorescent Antibody Technique; D005727:Ganglia, Spinal / Q000473:pathology*; D006561:Herpes Simplex / Q000473:pathology*; D008564:Membrane Potentials; D009474:Neurons / Q000502:physiology*; D009475:Neurons, Afferent / Q000382:microbiology; D051381:Rats; D011919:Rats, Inbred Strains; D018139:Simplexvirus; D013997:Time Factors; D014779:Virus Replication
D000212:Acyclovir