Abstract:
:Neurons in thalamic midline and paraventricular nuclei (PVT) display a unique slow afterhyperpolarizing potential (sAHP) following the low threshold spike (LTS) generated by activation of their low voltage Ca(2+) channels. We evaluated the conductances underlying this sAHP using whole-cell patch-clamp recordings in rat brain slice preparations. Initial observations recorded in the presence of TTX revealed a marked dependency of the LTS-induced sAHP on extracellular Na(+): replacing Na(+) with TRIS(+) in the external medium eliminated the LTS-induced sAHP; substitution of Na(+) with either Li(+) or choline(+) in the external medium resulted in a gradual loss of the sAHP and its replacement with a prolonged slow afterdepolarizing potential (sADP). The LTS-induced sAHP was reduced by quinidine and potentiated by loxapine, suggesting involvement of KNa-like channels. Canonical transient receptor potential (TRPC) channels were considered the source for Na(+) based on observations that the sAHP was suppressed by nonselective TRPC channel blockers (2-APB, flufenamic acid and ML204) but unchanged in the presence of TRPV1 channel blocker (SB-366791). In addition, after replacement of Na(+) with Li(+), the isolated LTS-induced sADP was significantly suppressed in the presence of 2-APB or ML204, after replacement of extracellular Ca(2+) with Sr(2+), and by intracellular Ca(2+) chelation with EGTA, data that collectively suggest involvement of Ca(2+)-activated TRPC-like conductances containing TRPC4/5 subunits. The isolated LTS-induced sADP also exhibited a strong voltage dependency, decreasing at hyperpolarizing potentials, further support for involvement of TRPC4/5 subunits. This sADP exhibited neurotransmitter receptor sensitivity, with suppression by 5-CT, a 5-HT7 receptor agonist, and enhancement by the neuropeptide orexin A. These data suggest that LTS-induced slow afterpotentials reflect a simultaneous interplay between KNa and TRPC-like conductances, novel for midline thalamic neurons.
journal_name
Neuropharmacologyjournal_title
Neuropharmacologyauthors
Kolaj M,Zhang L,Renaud LPdoi
10.1016/j.neuropharm.2014.06.023subject
Has Abstractpub_date
2014-11-01 00:00:00pages
88-96eissn
0028-3908issn
1873-7064pii
S0028-3908(14)00245-7journal_volume
86pub_type
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