AJP - Cell Physiology, Vol 258, Issue 6 C1086-C1091, Copyright © 1990 by American Physiological Society
Regulation of inositol 1,4,5-trisphosphate-induced Ca2+ release. II. Effect of cAMP-dependent protein kinase
P. Volpe and B. H. Alderson-Lang
Department of Physiology and Biophysics, University of Texas Medical Branch, Galveston 77550.
The effect of adenosine 3',5'-cyclic monophosphate (cAMP)-dependent protein
kinase (PKA) on Ca2+ loading, inositol 1,4,5-trisphosphate (IP3)-induced
Ca2+ release, and [3H]IP3 binding of canine cerebellar membrane fractions
was investigated. PKA in the presence of cAMP and the catalytic subunit of
PKA did not change Ca2+ loading yet increased the extent of IP3-induced
Ca2+ release by approximately 35%. Hill plot analysis indicated that the
catalytic subunit of PKA increased the apparent Michaelis constant of
IP3-induced Ca2+ release twofold, from 0.3 to 0.7 microM IP3. The protein
kinase inhibitor reversed these changes. cAMP affected neither Ca2+ loading
nor IP3-induced Ca2+ release. The catalytic subunit of PKA did not
appreciably affect the maximum binding and dissociation constant of [3H]IP3
binding, as judged by Scatchard analysis. Thus the catalytic subunit of PKA
influences the opening of Ca2+ channels by IP3 without interfering with the
binding of IP3 to its receptor sites.
