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 (IT ) was -474.61±48.33pA and IT density was -29.11±1.93pA/pF. The IT peak and IT 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 IT 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.