Muscarinic Agonists Cause Calcium Influx and Calcium Mobilization in Forebrain Neurons In Vitro

Abstract: We have examined the effects of the muscarinic agonist carbachol on the intracellular free Ca²⁺ concentration ([Ca²⁺]_i) in primary cultures of neurons from rat forebrain using the Ca²⁺‐sensitive fluorescent dye fura‐2. Addition of carbachol increased the [Ca²⁺]_i in ∼60% of cells studied. Oxotremorine‐M, but not pilocarpine, mimicked the effects of carbachol. The response was reduced by 60% on removal of extracellular Ca²⁺, a finding suggesting that muscarinic receptor activation causes Ca²⁺ influx in addition to intracellular Ca²⁺ mobilization. Tetrodotoxin and nitrendipine also significantly reduced the response to carbachol. These studies suggest that the changes in [Ca²⁺]_i produced by activation of muscarinic receptors result in part from mobilization of intracellular Ca²⁺ and that influx through voltage‐sensitive Ca²⁺ channels also provides a significant contribution to the net [Ca²⁺]_i change observed