Mechanism of spontaneous and receptor-controlled electrical activity in pituitary somatotrophs: experiments and theory.

  • Tsaneva-Atanasova K
  • Sherman A
  • van Goor F
 et al. 
  • 28

    Readers

    Mendeley users who have this article in their library.
  • 61

    Citations

    Citations of this article.

Abstract

Cultured pituitary somatotrophs release growth hormone in response to spontaneous Ca(2+) entry through voltage-gated calcium channels (VGCCs) that is governed by plateau-bursting electrical activity and is regulated by several neurohormones, including GH-releasing hormone (GHRH) and somatostatin. Here we combine experiments and theory to clarify the mechanisms underlying spontaneous and receptor-controlled electrical activity. Experiments support a role of a Na(+)-conducting and tetrodotoxin-insensitive channel in controlling spontaneous and GHRH-stimulated pacemaking, the latter in a cAMP-dependent manner; an opposing role of spontaneously active inwardly rectifying K(+) (K(ir)) channels and G-protein-regulated K(ir) channels in somatostatin-mediated inhibition of pacemaking; as well as a role of VGCCs in spiking and large conductance (BK-type) Ca(2+)-activated K(+) channels in plateau bursting. The mathematical model is compatible with a wide variety of experimental data involving pharmacology and extracellular ion substitution and supports the importance of constitutively active tetrodotoxin-insensitive Na(+) and K(ir) channels in maintaining spontaneous pacemaking in pituitary somatotrophs. The model also suggests that these channels are involved in the up- and downregulation of electrical activity by GHRH and somatostatin. In the model, the plateau bursting is controlled by two functional populations of BK channels, characterized by distance from the VGCCs. The rapid activation of the proximal BK channels is critical for the establishment of the plateau, whereas slow recruitment of the distal BK channels terminates the plateau.

Get free article suggestions today

Mendeley saves you time finding and organizing research

Sign up here
Already have an account ?Sign in

Find this document

Authors

  • Krasimira Tsaneva-Atanasova

  • Arthur Sherman

  • Frederick van Goor

  • Stanko S Stojilkovic

Cite this document

Choose a citation style from the tabs below

Save time finding and organizing research with Mendeley

Sign up for free