[Abstract Title]. - Society for Neuroscience

Program#/Poster#: 240.5/E27
Topic: B.10.b. Modulation of neuronal firing properties
Support: Epilepsy Foundation
Postdoctoral Research Abroad Program, National Science Council of Taiwan (NSC-
095-SAF-I-564-611-TMS)
Title: Mild hyperthermia induces intrinsic firing of CA1 pyramidal neurons
Authors: *H.-J. YAU, M. MARTINA;
Dept. of Physiol., Northwestern Univ., Chicago, IL
Abstract: Febrile seizures are the most frequent type of seizures, affecting 3-5 % of children
between 6 months and 3 years of age; yet, the detailed cellular mechanisms of febrile seizures
remain unclear. To increase our knowledge of such mechanisms, we studied the effect of
hyperthermia on the electrophysiologic properties of hippocampal pyramidal neurons.
Extracellular (loose-seal) and whole cell recordings obtained from CA1 pyramidal neurons
showed that mild hyperthermia (39-40°C) depolarizes ~95% of the pyramidal cells and induces
spontaneous firing in ~70 % of the cases, even in the absence of fast synaptic transmission,
suggesting an effect on intrinsic neuronal properties. Hyperthermia-induced depolarization was
still present after pharmacological blockade of voltage-gated channels and it was paralleled by a
decrease in membrane resistance, suggesting that the depolarizing response is mediated by the
activation of a temperature-dependent background conductance. These data suggest the possible
involvement of TRPV channels. Indeed, the TRPV blocker ruthenium red increased the input
resistance in ~40 % of pyramidal cells recorded at >37°C, while it was ineffective at 30-32°C,
confirming that TRPV channels are expressed in pyramidal neurons and open at febrile
temperature. Although hyperthermia depolarized ~95 % of the pyramidal cells, in ~40 % of the
cells a biphasic response was detected, in which a transient hyperpolarization preceded the
depolarization. This result suggests that other types of temperature-sensitive channels (possibly
potassium selective) are also present in these cells and mediate the hyperpolarization. Thus, we
tested the effect of flufenamic acid, an agonist of temperature-dependent KCNK channels, on the
hyperthermic response of CA1 pyramidal neurons. Flufenamic acid potentiated a temperaturedependent
potassium conductance and completely abolished hyperthermia-induced intrinsic
firing.
These results show that temperature sensitive ion channels mediate the response of pyramidal
neurons to hyperthermia and may constitute new targets for pharmacological treatment of febrile
seizures.
Disclosures: H. Yau, None; M. Martina, None.
Poster