Inositol 1,4,5-trisphosphate receptors in the endoplasmic reticulum: A single-channel point of view

• InsP3R single-channel properties studied by nuclear patch clamping are reviewed.
• We examine InsP3R K+ conductance and unitary Ca2+ current in physiological solutions.
• Steady-state Ca2+ and InsP3 dependencies of channels of various isoforms are compared.
• Ligand-regulated modal gating and graded recruitment of InsP3R channels are examined.
• Responses of InsP3R channels to abrupt ligand concentration changes are presented.

As an intracellular Ca2+ release channel at the endoplasmic reticulum membrane, the ubiquitous inositol 1,4,5-trisphosphate (InsP3) receptor (InsP3R) plays a crucial role in the generation, propagation and regulation of intracellular Ca2+ signals that regulate numerous physiological and pathophysiological processes. This review provides a concise account of the fundamental single-channel properties of the InsP3R channel: its conductance properties and its regulation by InsP3 and Ca2+, its physiological ligands, studied using nuclear patch clamp electrophysiology.

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