Membrane potential modulation of ionomycin-stimulated Ca2+ entry via Ca2+/H+ exchange and SOC in rat submandibular acinar cells

Abstract

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.

Control of PTH secretion by the TRPC1 ion channel

“…Knockdown of Orai1 did not affect PTH secretion. The positive effect of constitutively active STIM1/Orai1 mutants on PTH release is consistent with the well-known role of SOCE channels in hormonal release, exocytosis, and mast cell degranulation (30). These data provided additional evidence that TRPC1 has a specific, essential, and sufficient role in suppressing PTH secretion in PTH-C1 cells and does so independently of its ability to enhance SOCE.…”

“…This conclusion is based on PTH secretion data, whereby overexpression or depletion of STIM1 or Orai1 did not affect PTH secretion in PTH-C1 cells and, furthermore, overexpression of constitutively active STIM1 and Orai1 identified in patients with Stormorken or a Stormorken-like syndrome, respectively, enhanced rather than suppressed PTH secretion. While this seems to be at odds with mild hypocalcemia reported in some patients with Stormorken (47), it is in agreement with the well-established role of SOCE channels in exocytosis and hormonal release (30). The hypocalcemia seen in patients with Stormorken could be due to secondary effects of STIM1R304W in tissues other than the PTG, such as the kidney or bone.…”

Nitric oxide synthesis stimulated by arachidonic acid accumulation via PPARα in acetylcholine‐stimulated gastric mucous cells

“…However, acetylsalicylic acid (ASA) did not increase the amount of NO released with or without ACh stimulation ACh stimulation (n = 4). Ionomycin at 10 μM increased [Ca 2+ ] i to an extremely high level (Yoshida et al, 2010). The increase in [Ca 2+ ] i stimulated by 10 μM ACh was larger than that stimulated by 1 μM ACh (Shimamoto et al, 2005;; hence, the amount of NO released is dependent on [Ca 2+ ] i .…”