Thyrotropin-releasing hormone-induced rise in cytosolic calcium and activation of outward K+ current monitored simultaneously in individual GH3B6 pituitary cells

• Published in: The Journal of biological chemistry 1988-12, Vol.263 (36), p.19570-19576
• Main Authors: Mollard, P, Vacher, P, Dufy, B, Winiger, B P, Schlegel, W
• Format: Article
• Language: English
• Subjects: Acyltransferases - genetics; Animals; Biological and medical sciences; Calcium - metabolism; Cell Line; Cell Membrane - drug effects; Cell Membrane - physiology; Cell physiology; Cytosol - drug effects; Cytosol - metabolism; Electric Conductivity; Fundamental and applied biological sciences. Psychology; Membrane and intracellular transports; Membrane Potentials - drug effects; Molecular and cellular biology; Pituitary Neoplasms; Potassium Channels - drug effects; Potassium Channels - physiology; Sulfurtransferases - genetics; Thyrotropin - pharmacology; Transaminases - genetics
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1016/S0021-9258(19)77674-1

Thyrotropin-releasing hormone (TRH) acts on pituitary cells to raise the cytosolic free Ca2+ concentration ([Ca2+]i) and causes simultaneously a transient hyperpolarization of the plasma membrane. The combination of the microfluorimetric monitoring of [Ca2+]i with electrophysiological recordings obtained using the patch clamp technique in its whole cell configuration, allows the analysis of the correlation between changes in [Ca2+]i and the alterations in ionic currents at the plasma membrane. It was shown that in the absence of hormone stimulation, a depolarization-induced change in steady state [Ca2+]i, as well as the internal perfusion with Ca2+ at microM levels at constant membrane potential led to the activation of outward K+ current. TRH stimulation resulted in a marked but transient rise in [Ca2+]i; concomitantly, there was an increase in membrane conductance and an enhancement of outward current. During the time course of an individual response, an excellent correlation between the changes in [Ca2+]i and those in conductance or current was observed. The relative changes of current and conductance during the TRH response were consistent with the activation of a single type of ionic current, the apparent reversal potential of which coincided with the equilibrium potential for K+. A strong correlation between the TRH-induced changes in [Ca2+]i and K+, conductance was demonstrated in a large number of cells with varied kinetic features: significant correlation coefficients were found both for the transition time from basal to maximal values (r = 0.85, p less than 0.001) as well as for the total duration of the responses (r = 0.68, p less than 0.002). It is concluded that during the early phase of TRH action, the hormone-induced rise in [Ca2+]i is the principal cause of enhanced K+ channel activation.