Linopirdine modulates calcium signaling and stimulus-secretion coupling in adrenal chromaffin cells by targeting M-type K+ channels and nicotinic acetylcholine receptors.

Adrenal chromaffin cells synthesize and release catecholamines and several other transmitters that play important physiological roles in the coordinated response to stress or danger. The main trigger for secretion is acetylcholine (ACh) released from splanchnic nerve terminals that activates nicotinic ACh receptors (nAChRs) on the chromaffin cells, causing membrane depolarization and Ca2+ entry primarily through voltage-gated Ca2+ channels (Ca-channels). G protein-coupled receptors (GPCRs) can also trigger secretion, and it has been suggested that closure of M-type K+ channels might contribute to this process.