Na-K-2Cl cotransporter and store-operated Ca2+ item in pacemaking by interstitial cells of Cajal (Biophysical Journal)

Pacemaker depolarization in interstitial cells of Cajal (ICC) is believed to be induced by Ca2+ transients and activation of Ano1 channels in the plasma membrane. However, block of SOCE (store-operated calcium item) or the Na-K-2Cl cotransporter (NKCC1) terminate pacemaker activity in ICC, indicating these transporters are involved in the initiation or maintenance of pacemaker activity. We hypothesized that SOCE contributes to pacemaker depolarization by maintaining [Ca2+] in the endoplasmic reticulum (ER), which is the underlying source of Ca2+ transients for activation of Ano1.