Effect of 17β-oestradiol on T-type calcium channels in the lateral habenula

Abstract

T-type calcium channels (T-channels) are critical for regulating neuronal excitability. Oestrogen alters neuronal excitability by modulating the expression of T-channels. The lateral habenula (LHb), as a link between the limbic system and midbrain structures, expresses T-channels and ERs. However, little is known about the role of oestrogen with respect to modulating T-channels in the LHb. In the present study, we investigated the distribution of T-channels in 3 LHb subregions (rostral, middle and caudal) in normal female rats. Next, we analysed the influence of 17β-oestradiol (E₂ ) on T-channels in the LHb in ovariectomised (OVX) rats (oil and E₂ groups) using whole-cell patch clamp recording and a real-time polymerase chain reaction (PCR). In normal rats, the results obtained showed that the peak of T-type calcium current (I_T ) was -474.61 ± 48.33 pA and I_T density was -29.11 ± 1.93 pA/pF. The I_T peak and I_T density on LHb neurones gradually decreased across the rostrocaudal axis. The neuronal firing pattern varied depending on the location: burst firing was dominant (53.85%) in the rostral LHb, whereas tonic firing was dominant (79.31%) in the caudal LHb. In OVX rats, real-time PCR analysis revealed that E₂ treatment decreased Cav3.3 mRNA expression in the caudal LHb. Patch clamp recording showed that E₂ treatment decreased the peak I_T and also reduced the low-threshold spikes (LTS) number, amplitude and width of LTS in the caudal LHb. Taken together, the results obtained in the present study suggest that E₂ may inhibit T-channel activity by selectively down-regulating Cav3.3 calcium channel in the caudal LHb, leading to reduced the possibility of burst firing.

Keywords: T-type calcium channels; lateral habenula; oestrogen; patch clamp.