Differential Effects of PLC-Coupled Receptors on Intracellular Calcium Oscillations in HEK293 Cells

In HEK293 cells two different types of PLC-coupled receptor, M3 muscarinic cholinergic and V1a vasopressin, generate intracellular calcium oscillations when activated with low, physiological concentrations of agonist. We investigated and characterized the underlying Ca2+ signaling mechanisms to determine if there are receptor specific effects in generating the Ca2+ signal and impacting downstream signaling processes. Activating M3 and V1a receptors generates intracellular Ca2+-oscillations that require extracellular Ca2+-entry to be sustained. While the Ca2+-oscillating pattern appears similar for each receptor type, our studies indicate that the Ca2+ signal characteristics and underlying mechanisms generating them are significantly different. The V1a response may represent a mechanism driven by fluctuations in PLC activity and IP3 production. The muscarinic response may represent a stochastic or random mechanism where the oscillatory control of Ca2+ release is a function of Ca2+diffusion and the sensitivity of the IP3R channel to [Ca2+]. The different signaling properties associated with each PLC-coupled receptor may have profound effects in driving downstream Ca2+-dependent cellular processes.