Submitted on January 18, 2007
Accepted on February 22, 2007
Somatostatin decreases voltage-gated Ca2+ currents in GH3 cells through activation of somatostatin receptor 2
Seung-Kwon Yang1, Helena C Parkington2, Jacques Epelbaum3, and Chen Chen1*
1 Endocrine Cell Biology, Prince Henry's Institute, Melbourne, Victoria, Australia; Physiology, Monash University, Melbourne, Victoria, Australia
2 Physiology, Monash University, Melbourne, Victoria, Australia
3 U.549, INSERM, paris, France
* To whom correspondence should be addressed. E-mail: chen.chen{at}princehenrys.org.
The secretion of growth hormone (GH) is inhibited by hypothalamic somatostatin (SRIF) in somatotropes through five subtypes of the somatostatin receptor (SSTRs1-5). We aimed to characterize the subtype(s) of SSTRs involved in the Ca2+ current reduction in GH3 somatotrope cells using specific SSTR subtype agonists. Nystatin-perforated patch clamp was used to record voltage-gated Ca2+ currents using a holding potential of -80mV in the presence of K+ and Na+ channel blockers. We first established the presence of T, L, N, and P/Q type Ca2+ currents in GH3 cells using a variety of channel blockers (Ni+, nifedipine, ω-conotoxin GVIA, and ω-agatoxin IVA). SRIF (200nM) reduced L- and N-type, but not T- or P/Q-type currents in GH3 cells. A range of concentrations of each specific SSTR agonist was tested on Ca2+ currents to find the maximal effective concentration. Activation of SSTR2 with 10-7M and 10-8M L-797,976 decreased the voltage-gated Ca2+ current and abolished any further decrease by SRIF. SSTR1, SSTR3, SSTR4, and SSTR5 agonists at 10-7M did not modify the voltage-gated Ca2+ current and did not affect the Ca2+ current response to SRIF. These results indicate that SSTR2 is mainly involved in regulating voltage-gated Ca2+ currents by SRIF, which contributes to the decrease in [Ca2+]i and GH secretion by SRIF.
