Ionic mechanism of the outward current induced by extracellular ejection of interleukin-1 onto identified neurons of Aplysia.
The ionic mechanism of the effect of extracellularly ejected recombinant human interleukin-1-beta (rhIL-1) on the membrane of identified neurons R9 and R10 of Aplysia was investigated with voltage-clamp, micropressure-ejection, and ion substitution techniques. Micropressure-ejected rhIL-1 caused a marked hyperpolarization in the unclamped neuron. Clamping the same neuron at its resting potential level (-60 mV) and reejecting rhIL-1 with the same dose produced a slow outward current (I0(IL-1), 20-30 s in duration, 3-5 nA in amplitude) associated with a decrease in input membrane conductance. I0(IL-1) was decreased by depolarization and increased by hyperpolarization. The extrapolated reversal potential of I0(IL-1) was approximately +15 mV. I0(IL-1) was sensitive to changes in the external Na+ concentration but not to changes in K+, Ca2+ and Cl- concentrations, and was resistant to tetraethylammonium (5 mM) and 4-aminopyridine (5 mM). Neither perfusion of the neuron with 50 microM tetrodotoxin nor perfusion with 10 mM Co2+ seawater caused any changes in I0(IL-1). I0(IL-1) was partially reduced by 50 microM ouabain. These results suggest that extracellular IL-1 can induce a slow outward current associated with a decrease in Na+ conductance and the immunomodulator IL-1 can act directly on the nervous system as well as on the immune system.
Sawada
M
M
Department of Physiology, Shimane Medical University, Izumo, Japan.
Hara
N
N
Maeno
T
T
D000818:Animals; D001048:Aplysia; D002118:Calcium / Q000494:pharmacology; D003035:Cobalt / Q000494:pharmacology; D004553:Electric Conductivity / Q000187:drug effects; D005071:Evoked Potentials / Q000187:drug effects; D005724:Ganglia / Q000502:physiology; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D011188:Potassium / Q000494:pharmacology; D011994:Recombinant Proteins / Q000494:pharmacology; D012623:Seawater
D007375:Interleukin-1; D011994:Recombinant Proteins; D003035:Cobalt; D011188:Potassium; D002118:Calcium