L-type Ca2+ channels and K+ channels specifically modulate the frequency and amplitude of spontaneous Ca2+ oscillations and have distinct roles in prolactin release in GH(3) cells
Ac. Charles et al., L-type Ca2+ channels and K+ channels specifically modulate the frequency and amplitude of spontaneous Ca2+ oscillations and have distinct roles in prolactin release in GH(3) cells, J BIOL CHEM, 274(11), 1999, pp. 7508-7515
GH(3) cells showed spontaneous rhythmic oscillations in intracellular calci
um concentration ([Ca2+](i)) and spontaneous prolactin release. The L-type
Ca2+ channel inhibitor nimodipine reduced the frequency of Ca2+ oscillation
s at lower concentrations (100nm-1 mu M), whereas at higher concentrations
(10 mu M), it completely abolished them. Ca2+ oscillations persisted follow
ing exposure to thapsigarsn, indicating that inositol 1,4,5-trisphosphate-s
ensitive intracellular Ca2+ stores were not required for spontaneous activi
ty. The K+ channel inhibitors Ba2+, Cs+, and tetraethylammonium (TEA) had d
istinct effects on different K+ currents, as well as on Ca2+ oscillations a
nd prolactin release. Cs+ inhibited the inward rectifier K+ current (K-IR)
and increased the frequency of Ca2+ oscillations. TEA inhibited outward Kcurrents activated at voltages above -40 mV (grouped within the category of
Ca2+ and voltage-activated currents, K-Ca,K-V) and increased the amplitude
of Ca2+ oscillations. Ba2+ inhibited both K-IR and K-Ca,K-V and increased
both the amplitude and the frequency of Ca2+ oscillations. Prolactin releas
e was increased by Ba2+ and Cs+ but not by TEA. These results indicate that
L-type Ca2+ channels and K-IR channels modulate the frequency of Ca2+ osci
llations and prolactin release, whereas TEA-sensitive K-Ca,K-V channels mod
ulate the amplitude of Ca2+ oscillations without altering prolactin release
. Differential regulation of these channels can produce frequency or amplit
ude modulation of calcium signaling that stimulates specific pituitary cell
functions.