Stretch-induced Ca(2+) release via an IP(3)-insensitive Ca(2+) channel

Area of Science:

• Cell Biology
• Physiology
• Biochemistry

Background:

• Mechanical stimuli, such as stretch, elevate intracellular calcium ([Ca(2+)](i)) in vascular smooth muscle cells (VSMC).
• A portion of this [Ca(2+)](i) increase originates from intracellular calcium stores.
• Understanding the mechanisms of calcium release from these stores under mechanical stress is crucial for vascular health.

Purpose of the Study:

• To investigate the effect of cyclical stretch on calcium release from intracellular stores in VSMC.
• To identify the specific intracellular calcium channels and pathways involved in stretch-induced calcium release.

Main Methods:

• Permeabilized VSMC were loaded with (45)Ca(2+) and subjected to cyclical stretch.
• The efflux of (45)Ca(2+) was measured under various conditions, including inhibition of IP(3), ryanodine, and NAADP channels.
• The effects of lanthanum, gadolinium, and cytochalasin D on calcium efflux were assessed.

Main Results:

• Cyclical stretch significantly increased the (45)Ca(2+) rate constant, indicating enhanced calcium release.
• Inhibition of inositol 1,4,5-trisphosphate (IP(3)), ryanodine, and nicotinic acid adenine dinucleotide phosphate (NAADP) channels did not affect stretch-induced calcium release.
• Lanthanum, gadolinium, and cytochalasin D, but not nocodazole, inhibited the increased calcium efflux.

Conclusions:

• A novel stretch-sensitive intracellular calcium store exists in VSMC.
• This store is distinct from the IP(3)-, ryanodine-, and NAADP-sensitive calcium stores.
• The findings suggest a new mechanism for mechanical force transduction in VSMC calcium signaling.