Membrane potential modulation of ionomycin-stimulated Ca(2+) entry via Ca (2+)/H (+) exchange and SOC in rat submandibular acinar cells.
Ionomycin (IM) at 5 microM mediates the Ca(2+)/H(+) exchange, while IM at 1 microM activates the store-operated Ca(2+) entry channels (SOCs). In this study, the effects of depolarization on both pathways were examined in rat submandibular acinar cells by increasing extracellular K(+) concentration ([K(+)](o)). IM (5 microM, the Ca(2+)/H(+) exchange) increased the intracellular Ca(2+) concentration ([Ca(2+)](i)) to an extremely high value at 151 mM [K(+)](o). However, with increasing [K(+)](o), the rates of Ca(2+) entry decreased in a linear relationship. The reversal potential (E (rev)) for the Ca(2+)/H(+) exchange was +93 mV, suggesting that IM (5 microM) exchanges 1 Ca(2+) for 1 H(+). Thus, depolarization decreases the Ca(2+) influx via the Ca(2+)/H(+) exchange because of its electrogenicity (1 Ca(2+) for 1 H(+)). On the other hand, IM (1 microM, the SOCs) abolished an increase in [Ca(2+)](i) at 151 mM [K(+)](o). With increasing [K(+)](o), the rate of Ca(2+) entry immediately decreased linearly. The E (rev) for the SOC was +3.7 mV, suggesting that the SOCs are nonselective cation channels and less selective for Ca(2+) over Na(+) (P (Ca)/P (Na) = 8.2). Moreover, an increase in extracellular Ca(2+) concentration (20 mM) enhanced the Ca(2+) entry via the SOCs at 151 mM [K(+)](o), suggesting depolarization does not inhibit the SOCs and decreases the driving force for the Ca(2+) entry. This suggests that membrane potential changes induced by a secretory stimulation finely regulate the [Ca(2+)](i) via the SOCs in rat submandibular acinar cells. In conclusion, IM increases [Ca(2+)](i) via two pathways depending on its concentration, the exchange of 1 Ca(2+) for 1 H(+) at 5 muM and the SOCs at 1 microM.
Yoshida
Hideyo
H
Central Research Laboratory (Nakahari Project), Osaka Medical College, 2-7 Daigaku-cho, Takatsuki, 569-8686, Japan.
Hirono
Chikara
C
Shimamoto
Chikao
C
Daikoku
Eriko
E
Kubota
Takahiro
T
Sugita
Makoto
M
Shiba
Yoshiki
Y
Nakahari
Takashi
T
D000818:Animals; D017920:Antiporters / Q000502:physiology*; D002118:Calcium / Q000032:analysis / Q000378:metabolism; D015220:Calcium Channels / Q000502:physiology*; D027682:Cation Transport Proteins / Q000502:physiology*; D015759:Ionomycin / Q000494:pharmacology*; D007476:Ionophores / Q000494:pharmacology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects* / Q000502:physiology; D011188:Potassium / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D013363:Submandibular Gland / Q000187:drug effects* / Q000502:physiology*
D017920:Antiporters; D015220:Calcium Channels; D027682:Cation Transport Proteins; D007476:Ionophores; C027614:calcium-hydrogen antiporters; D015759:Ionomycin; D011188:Potassium; D002118:Calcium