Conversion between permeability states of IP3 receptors in cultured smooth muscle cells.
The kinetics of the effect of inositol 1,4,5-trisphosphate (IP3) on Ca2+ in the sarcoplasmic reticulum (SR) were studied in saponin-permeabilized A7r5 cells. At 0.1 microM, IP3 elicited slow monoexponential declines in SR free Ca2+ concentration ([Ca2+]SR). For IP3 concentration ([IP3]) = 0.2-100 microM, evoked declines in [Ca2+]SR were biphasic and best fit as the sum of two first-order processes with rate constants kfast and kslow. The kfast varied as a function of [IP3] over the range tested, whereas kslow was already maximal when [IP3] = 0.1 microM. To analyze SR Ca2+ release elicited by IP3, the rate constants for IP3-induced changes in the total SR Ca2+ content (kR) were calculated. kR was accurately described only when both [Ca2+]SR and [IP3] were considered together. kR was dependent on IP3 binding to receptors that existed in either of two states, a high-affinity low-conductance state (IP3RH) and a low-affinity high-conductance state (IP3RL). The permeability of IP3RL was 12.28 times larger than that of IP3RH, and the conversion between permeability states as well as changes in both the affinity and cooperativity with which IP3 was bound to IP3RL were mediated by SR Ca2+. This SR Ca(2+)-dependent modulation of the characteristics of IP3 receptors forms the basis for the biphasic time course characteristic of IP3-evoked SR Ca2+ release.
Sugiyama
T
T
Department of Physiology, University of Maryland School of Medicine, Baltimore, USA.
Goldman
W F
WF
D000818:Animals; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism*; D002478:Cells, Cultured; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D053496:Inositol 1,4,5-Trisphosphate Receptors; D008954:Models, Biological; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D009994:Osmolar Concentration; D010539:Permeability; D051381:Rats; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D012519:Sarcoplasmic Reticulum / Q000378:metabolism
D015220:Calcium Channels; D053496:Inositol 1,4,5-Trisphosphate Receptors; D018160:Receptors, Cytoplasmic and Nuclear; D015544:Inositol 1,4,5-Trisphosphate; D002118:Calcium