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 ( LH b), 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 LH b. In the present study, we investigated the distribution of T‐channels in 3 LH b subregions (rostral, middle and caudal) in normal female rats. Next, we analysed the influence of 17β‐oestradiol (E 2 ) on T‐channels in the LH b in ovariectomised ( OVX ) rats (oil and E 2 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 LH b 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 LH b, whereas tonic firing was dominant (79.31%) in the caudal LH b. In OVX rats, real‐time PCR analysis revealed that E 2 treatment decreased Cav3.3 mRNA expression in the caudal LH b. Patch clamp recording showed that E 2 treatment decreased the peak I T and also reduced the low‐threshold spikes ( LTS ) number, amplitude and width of LTS in the caudal LH b. Taken together, the results obtained in the present study suggest that E 2 may inhibit T‐channel activity by selectively down‐regulating Cav3.3 calcium channel in the caudal LH b, leading to reduced the possibility of burst firing.