Acetylcholine-evoked calcium mobilization and ion channel activation in human labial gland acinar cells from patients with primary Sjogren's syndrome

Recent evidence has indicated that the salivary gland dysfunction associate d with Sjogren's syndrome (SjS) is not necessarily due to immune-mediated d estruction of acinar tissue. SjS sufferers may possess substantial reserves of acinar tissue but nevertheless be incapable of maintaining salivary flo w rates in the normal range. We have investigated the ability of isolated l abial gland acinar cells from SjS patients to fluid secrete by measuring ag onist-evoked changes in intracellular Ca2+ ([Ca2+](i)) using fura-2 microfl uorimetry and activation of K+ and Cl- channels using the patch-clamp whole cell technique. We can confirm that stimulation with a super-maximal dose of acetylcholine (ACh) increased [Ca2+](i) equally in both control acinar c ells and those derived from SjS patients. However, at submaximal concentrat ions, the dose-response curve for ACh was shifted to the right by approxima tely one order of magnitude in acinar cells from SjS patients compared to c ontrol acinar cells. Patch-clamp measurements consistent with the presence of Ca2+-activated K+ and Cl- conductances were obtained from both control a cinar cells and those obtained from SjS patients. Dose-dependent activation of the ion channels by acetylcholine was also right-shifted in acinar cell s from SjS patients compared to control cells. Our data show that labial gl and acinar cells from SjS patients were capable of responding to agonist st imulation by mobilizing [Ca2+](i) and activating K+ and Cl- channels consis tent with the requirements of fluid secretion. However, the persistent loss of sensitivity to ACh observed in from SjS patients may account for the la ck of saliva production observed in these patients in vivo.