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Published on: November 3, 2020
Unitary Ca(2+) current through recombinant type 3 InsP(3) receptor channels under physiological ionic conditions
Horia Vais1, J Kevin Foskett, Don-On Daniel Mak
1Department of Physiology and 2 Department of Cell and Developmental Biology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
Researchers measured the unitary calcium current (i(Ca)) through inositol 1,4,5-trisphosphate (InsP(3)) receptor channels under physiological conditions. This finding helps understand how calcium signals regulate cellular processes.
Area of Science:
- Cellular Biology
- Biophysics
- Physiology
Background:
- Inositol 1,4,5-trisphosphate (InsP(3)) receptors (InsP(3)Rs) are crucial for intracellular calcium (Ca2+) signaling.
- The unitary Ca2+ current (i(Ca)) through InsP(3)Rs influences Ca2+ release dynamics, but has not been measured under physiological conditions.
Purpose of the Study:
- To report the first direct measurement of i(Ca) through an InsP(3)R channel in its native membrane environment.
- To investigate the conductance properties of InsP(3)R channels under physiological ionic conditions.
Main Methods:
- Nuclear patch clamp electrophysiology was employed.
- Rapid perfusion solution exchanges facilitated the study.
- Recombinant homotetrameric rat type 3 InsP(3)R channels were utilized.
Main Results:
- The i(Ca) was measured under physiological ranges of [Ca2+]ER, [Ca2+]i, and [Mg2+]f.
- A linear i(Ca)-[Ca2+]ER relationship was observed, independent of [Mg2+]f.
- Measured i(Ca) was 0.15 ± 0.01 pA for a filled ER store with 500 μM [Ca2+]ER.
Conclusions:
- Ca2+ released by InsP(3)R channels can locally elevate cytoplasmic Ca2+ to levels sufficient for activating neighboring InsP(3)Rs.
- This supports the mechanism of Ca2+-induced Ca2+ release, crucial for cellular signaling.
- The findings provide essential data for modeling InsP(3)R-mediated Ca2+ signaling.
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