Ca2+ sensitivity of the maxi chloride channel in interstitial cells of Cajal

Background Interstitial cells of Cajal (ICC) associated with the myenteric plexus of the small intestine express maxi chloride channels. Our aim was to investigate whether or not these channels would be activated by increases in intracellular Ca²⁺, as that would strengthen evidence for their potential role in ICC pacemaking. A further aim was to examine whether inwardly and outwardly rectifying maxi chloride currents signify different channels. Methods We used Fluo‐4 AM Ca²⁺ imaging and patch clamp electrophysiology (cell‐attached and inside‐out) on isolated ICC in short term culture. Key Results Increasing intracellular Ca²⁺ by three functionally distinct mechanisms (blocking sarcoplasmic reticulum Ca²⁺ refilling, creating membrane Ca²⁺ pores and a solution designed to block plasmalemmal Ca²⁺ extrusion) was followed by inwardly rectifying maxi chloride channel activation assessed in the cell‐attached configuration. Furthermore, in the inside‐out configuration, increased outwardly rectifying maxi‐chloride channel activity followed an increase in Ca²⁺ to 2 mmol L^?1 at the cytoplasmic face of the channel. Conclusions & Inferences Increase in intracellular Ca²⁺ will activate the maxi chloride channels. Maxi chloride currents are inwardly rectifying in the cell‐attached patch clamp configuration under physiological conditions and are outwardly rectifying in the inside‐out configuration. The same channel is responsible for both currents. Ca²⁺ does not appear to regulate the rectification.