The relative order of IP3 sensitivity of types 1 and 3 IP3 receptors is pH dependent.
The type-3 inositol 1,4,5-trisphosphate (IP3) receptor, in contrast to the type-1 IP3 receptor (IP3R), is not stimulated by sulfhydryl oxidation and is less sensitive to adenosine 5'-triphosphate. In the present study we compared the effect of pH on the Ca2+ release induced by IP3 and cytosolic Ca2+ between IP3R3-expressing 16HBE14o- cells and IP3R1-expressing A7r5 cells. Changing pH from 6.8 to 7.5 decreased the IP3 concentration required for half-maximal stimulation of IP3R3 (EC50) 10.7-fold (from 2.14 to 0.20 microM). Similar alkalinization decreased the IP3 concentration (EC50) for stimulation of IP3R1 only 2.5-fold (from 0.87 to 0.35 microM). IP3R1 is therefore the more sensitive isoform at pH 6.8, while IP3R3 is more sensitive at pH 7.5. Stimulation and inhibition of IP3R1 and -3 by low and high cytosolic [Ca2+] respectively was observed at both pH 6.8 and 7.5. Increasing [H+] shifted the Ca2+-activation curve of IP3R1 towards higher [Ca2+] but did not affect the Ca2+ dependence of IP3R3. We conclude that IP3R1 and -3 differ markedly in their response to protons.
De Smet
P
P
Laboratorium voor Fysiologie, K. U. Leuven Campus Gasthuisberg O/N, Herestraat 49, B-3000 Leuven, Belgium.
Parys
J B
JB
Vanlingen
S
S
Bultynck
G
G
Callewaert
G
G
Galione
A
A
De Smedt
H
H
Missiaen
L
L
D000818:Animals; D001011:Aorta / Q000196:embryology; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000502:physiology*; D002460:Cell Line; D006863:Hydrogen-Ion Concentration; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D053496:Inositol 1,4,5-Trisphosphate Receptors; D010539:Permeability; D051381:Rats; D018160:Receptors, Cytoplasmic and Nuclear / Q000502:physiology*
D015220:Calcium Channels; D053496:Inositol 1,4,5-Trisphosphate Receptors; D018160:Receptors, Cytoplasmic and Nuclear; D015544:Inositol 1,4,5-Trisphosphate; D002118:Calcium