Kinetic basis of quantal calcium release from intracellular calcium stores.
The kinetics of Ca2+ release from canine cerebellum and rabbit skeletal muscle microsomes, mediated by the inositol 1,4,5-trisphosphate (IP3) receptor (IRC) and the ryanodine receptor (RyRC), respectively, were analyzed by a model, which considers that Ca2+ release channels undergo spontaneous inactivation. We found that: (i) both the initial rate of release (Vo) and the rate of inactivation (Vi) were saturable functions of the activating ligand concentration (CL); and (ii) the ratio of Vi/Vo, termed the relative tendency for inactivation, decreased with increasing CL. Equilibrium [3H]-IP3 binding studies, on the other hand, revealed the presence of one single class of non-co-operative IP3 sites in cerebellum membranes (Kdeq = 47 nM and Hill coefficient = 1.1). Based on the above Vi-Vo relationship and the IP3-binding data, we propose that quantal Ca2+ release through IRCs might be a result of spontaneous channel inactivation, whose rate is controlled by the ratio of IP3-occupied/free monomers in the tetrameric release channel units. Furthermore, because of the kinetic similarities between the IRC- and RyRC-mediated Ca2+ release processes, as well as between quantal Ca2+ release and channel adaptation, the same mechanism is also proposed to apply to the RyRC-mediated Ca2+ release as well as to constitute the basis of release channel adaptation.
Mészáros
L G
LG
Department of Physiology and Endocrinology, Medical College of Georgia, Augusta, USA.
Zahradnikova
A
A
Volpe
P
P
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism*; D002531:Cerebellum / Q000737:chemistry / Q000378:metabolism*; D002614:Chelating Agents / Q000494:pharmacology; D004285:Dogs; D018492:Dopamine Antagonists / Q000494:pharmacology; D004533:Egtazic Acid / Q000494:pharmacology; D004734:Energy Metabolism / Q000502:physiology; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism / Q000494:pharmacology; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology; D007700:Kinetics; D008861:Microsomes / Q000378:metabolism; D018482:Muscle, Skeletal / Q000737:chemistry / Q000378:metabolism*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011817:Rabbits; D011869:Radioligand Assay; D014268:Trifluoperazine / Q000494:pharmacology; D014316:Tritium
D015220:Calcium Channels; D002614:Chelating Agents; D018492:Dopamine Antagonists; D010726:Phosphodiesterase Inhibitors; D014316:Tritium; D014268:Trifluoperazine; D002110:Caffeine; D004533:Egtazic Acid; D015544:Inositol 1,4,5-Trisphosphate; D000255:Adenosine Triphosphate; D002118:Calcium