Inhibition of N‐ and P/Q‐type calcium channels by postsynaptic GABAB receptor activation in rat supraoptic neurones

Open Access
Publisher Website
Google Scholar
Abstract
1 Voltage‐dependent Ca2+ currents of dissociated rat supraoptic nucleus (SON) neurones were measured using the whole‐cell configuration of the patch‐clamp technique to examine direct postsynaptic effects of GABAB receptor activation on SON magnocellular neurones. 2 The selective GABAB agonist baclofen reversibly inhibited voltage‐dependent Ca2+ currents elicited by voltage steps from a holding potential of −80 mV to depolarized potentials in a dose‐dependent manner. The ED50 of baclofen for inhibiting Ca2+ currents was 1.4 × 10−6 M. Baclofen did not inhibit low threshold Ca2+ currents elicited by voltage steps from −120 to −40 mV. 3 Inhibition of high threshold Ca2+ currents by baclofen was rapidly and completely reversed by the selective GABAB antagonists, CGP 35348 and CGP 55845A, when the antagonists were added at the molar ratio vs. baclofen of 10 : 1 and 0.01 : 1, respectively. It was also reversed by a prepulse to +150 mV lasting for 100 ms. 4 The inhibition of Ca2+ currents was abolished when the cells were pretreated with pertussis toxin for longer than 20 h or with N‐ethylmaleimide for 2 min. It was also abolished when GDPβS was included in the patch pipette. When GTPγS was included in the patch pipette, baclofen produced irreversible inhibition of Ca2+ currents and this inhibition was again reversed by the prepulse procedure. 5 The inhibition of N‐, P/Q‐, L‐ and R‐type Ca2+ channels by baclofen (10−5 M) was 24.1, 10.5, 3.1 and 3.6 %, respectively, of the total Ca2+ currents. Only the inhibition of N‐ and P/Q‐types was significant. 6 These results suggest that GABAB receptors exist in the postsynaptic sites of the SON magnocellular neurones and mediate selective inhibitory actions on voltage‐dependent Ca2+ channels of N‐ and P/Q‐types via pertussis toxin‐sensitive G proteins, and that such inhibitory mechanisms may play a role in the regulation of SON neurones by the GABA neurones.