Estrogen upregulates T-type calcium channels in the hypothalamus and pituitary.
Low voltage-activated (T-type) Ca2+ channels are responsible for generating low-threshold spikes (LTS) that facilitate burst firing and transmitter release in neurons. The T-type Ca2+ channels contain a regulatory alpha1 subunit, and several isoforms of the alpha1 subunit (Cav3.1, 3.2, 3.3) have been cloned. The Cav 3.1 alpha1 subunit is abundantly expressed in the hypothalamus. Previously, we found that 17 beta-estradiol (E2) increased the number of arcuate neurons expressing LTS. Therefore, we used an ovariectomized female guinea pig model to measure the distribution and regulation of Cav3.1 mRNA expression by E2. Guinea pig Cav3.1 alpha1 subunit sequences, which were cloned by PCR, were used in ribonuclease protection (RPA) and in situ hybridization assays to evaluate mRNA expression. Based on a RPA, E2 significantly increased the mRNA expression of Cav3.1 alpha1 subunit in the mediobasal hypothalamus and the pituitary. In situ hybridization analysis revealed that E2 significantly increased Cav 3.1 mRNA expression in medial preoptic nuclei, bed nuclei stria terminalis, and the arcuate nucleus. Whole-cell patch recordings in arcuate neurons revealed that E2 treatment significantly increased the peak T-type Ca2+ current density by twofold without affecting the activation/inactivation characteristics and augmented the rebound excitation by threefold to fourfold. These results suggest that estrogen regulates the mRNA expression of T-type calcium channels, which leads to increased functional expression of the channel. Increased expression of T-type channels could be one mechanism by which estrogen augments burst firing and transmitter release in hypothalamic neurons.
Qiu
Jian
J
Department of Physiology and Pharmacology, Oregon National Primate Research Center, Oregon Health and Science University, Portland, Oregon 97239-3098, USA.
Bosch
Martha A
MA
Jamali
Khalid
K
Xue
Changhui
C
Kelly
Martin J
MJ
Rønnekleiv
Oline K
OK
D000818:Animals; D020747:Calcium Channels, T-Type / Q000096:biosynthesis* / Q000235:genetics; D004958:Estradiol / Q000378:metabolism / Q000494:pharmacology*; D005260:Female; D006168:Guinea Pigs; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism*; D010052:Ovariectomy; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology*
C121855:CACNA1G protein, human; D020747:Calcium Channels, T-Type; D004958:Estradiol