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A novel receptor-operated Ca2+-permeable channel activated by ATP in smooth muscle

Abstract

Receptor-operated Ca2+ entry has been proposed as a signalling mechanism in many cells1–8. Receptor-operated Ca2+ channels (ROCs) were first postulated in smooth muscle by Bolton2, van Breemen3 and Somlyo and Somlyo4, but recordings of directly ligand-gated Ca2+ current are lacking. Here we describe receptor-operated Ca2+ current evoked in arterial smooth muscle cells by ATP, a sympathetic neurotransmitter9. ATP activates channels with approximately 3:1 selectivity for Ca2+ over Na+ at near-physiological concentrations and with a unitary conductance of 5 pS in 110 mM Ca2+ or Ba2+. The channels can be opened even at very negative potentials and resist inhibition by cadmium or nifedipine, unlike voltage-gated Ca2+ channels; they are not blocked by Mg2+, unlike NMD A (N-methyl-D-asparate)-activated channels10,11; they are directly activated by ligand, without involvement of readily diffusible second messengers, unlike cation channels in neutrophils12 and T lymphocytes13. Thus, the ATP-activated channels provide a distinct mechanism for excitatory synaptic current and Ca2+ entry in smooth muscle.

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References

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Benham, C., Tsien, R. A novel receptor-operated Ca2+-permeable channel activated by ATP in smooth muscle. Nature 328, 275–278 (1987). https://doi.org/10.1038/328275a0

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