Abstract | 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 μM) 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 μM 2-methyl-thio ATP (MeS-ATP) and UTP revealed that P2Y receptor activation underlies this response. The calcium influx pathway responsible for the sustained calcium response was inhibited by metal ions. In both cell types La3+ and Zn2+ (100 μM) effectively inhibited the plateau phase of the response, whilst 100 μM Ni2+ had little or no effect. In conclusion, P2Y 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 mGlu5 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. |
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