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 cells^1–8. 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 channels^10,11; 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.