Cytosolic calcium levels ([Ca2+]i) in pituitary cells are controlled by three families of plasma membrane and endoplasmic reticulum (ER) calcium channels; voltage-, ATP- and InsP3-gated. All anterior pituitary cells generates spontaneous and extracellular Ca2+-dependent [Ca2+]i transients through L- and T-type voltage-gated Ca2+ channels. In lactotrophs and somatotrophs, but not gonadotrophs, thyrotrophs, and corticotrophs, the spontaneous electrical activity is coupled to hormone secretion. Pituitary cells also express at least two types of P2X purinergic cationic channels. Somatotrophs express wild-type P2X2 channels and several splice variants, whereas gonadotrophs and lactotrophs express a wild-type and spliced forms of P2X5 channels. The native purinergic channels in pituitary cells are heteropolymers of the cloned subunits, activation of which depolarizes the cells. This lead to an increase in the frequency of action potentials, a rise in [Ca2+]i and an increase in basal hormone secretion. Activation of IP3-gated Ca2+ release channels is associated with a non-oscillatory amplitude-modulated [Ca2+]i responses in lactotrophs and somatotrophs, and oscillatory frequency-modulated [Ca2+]i responses in gonadotrophs and thyrotrophs. In gonadotrophs, the conductivity of ER calcium channels is also controlled by Ca2+, which exerts both facilitatory and inhibitory actions that lead to periodic Ca2+ release from the ER. Such release activates apamin-sensitive and -resistant potassium currents. The former are responsible for cessation of action potential firing, due to transient hyperpolarization, and the latter for gradual depolarization that leads to a bursting pattern of electrical activity. Conversely, Ca2+ influx through L-type and P2X channels facilitates Ca2+ release from the ER by a direct and instantaneous action on the release mechanism, and magnifies the Ca2+ signals due to its gradual effect on the reloading of ER pool. The coordinate actions of these Ca2+ channels permit the generation of long-lasting [Ca2+]i signals in agonist-stimulated cells.
This is joint work with T. Koshimizu, F. Van Goor, and M. Tomic.
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