Purinergic and muscarinic receptor activation activates a common calcium entry pathway in rat neocortical neurons and glial cells.

The nature of metabotropic purinergic and muscarinic receptor-mediated increases in intracellular calcium in primary rat neocortical neurons and glial cells has been investigated using fluorescence imaging techniques. Bath-application of ATP and muscarine (10 microM) elicited a characteristic increase in intracellular calcium in both neurons and glial cells. The profile of this response consisted of an initial transient increase followed by a sustained elevation (the plateau phase) which was dependent on extracellular calcium. Examination of the pharmacological basis of the purinergic receptor-mediated calcium response using 10 microM 2-methyl-thio ATP (MeS-ATP) and UTP revealed that P(2Y) receptor activation underlies this response. The calcium influx pathway responsible for the sustained calcium response was inhibited by metal ions. In both cell types La(3+) and Zn(2+) (100 microM) effectively inhibited the plateau phase of the response, whilst 100 microM Ni(2+) had little or no effect. In conclusion, P(2Y) purinergic and muscarinic receptor activation evoke a sustained increase in intracellular calcium in neocortical neurons and glial cells. This response has similar characteristics to that we have previously described following mGlu(5) activation. We propose that in these cell types stimulation of metabotropic receptors coupled to phosphoinositide turnover activates a common calcium entry pathway that is distinct from voltage-gated calcium channels and resembles store-operated calcium entry.