1 Kv 1 . 3 channels regulate synaptic transmission in the nucleus of 2 solitary tract 3 4

25 The voltage-gated potassium channel, Kv1.3 has been reported to regulate transmitter 26 release in select central and peripheral neurons. In this study we evaluated its role at 27 the synapse between visceral sensory afferents and secondary neurons in the nucleus 28 of the solitary tract (nTS). We identified mRNA and protein for Kv1.3 in rat nodose 29 ganglia (NG) using RT-PCR and Western blot analysis. In immunohistochemical 30 studies, anti-Kv1.3 immunoreactivity was very strong in internal organelles in the soma 31 of nodose neurons with weaker distribution near the plasma membrane. Anti-Kv1.3 was 32 also identified in the axonal branches that project centrally including their presynaptic 33 terminals in the medial and commissural nTS. In current clamp studies margatoxin 34 (MgTx), a high affinity blocker of Kv1.3, produced an increase in action potential 35 duration in C-type but not in A-or Ah-type neurons. To evaluate the role of Kv1.3 at the 36 presynaptic terminal we examined the effect of MgTx on tract evoked monosynaptic 37 excitatory postsynaptic currents (eEPSCs) in brain slices of the nTS. MgTx increased 38 the amplitude of the eEPSC in a subset of neurons with the major increase occurring 39 during the first stimuli in a 20 Hz train. These data together with the results from somal 40 3 recordings support the hypothesis that Kv1.3 regulates the duration of the action 41 potential in presynaptic terminal of C fibers limiting transmitter release to the 42 postsynaptic cell. 43 44 45