Plate Nº 52 · recorded October 20, 2026
Health & Medicine ResearchReported finding
Statin muscle pain traced to three-molecule calcium channel attack
UBC researchers captured an atom-level view of how three statin molecules cooperate to lock open the RyR1 calcium channel in skeletal muscle, identifying the molecular source of statin-related muscle pain for the first time.
By Marcus Bennett3 min read539 words
In brief
- Published in Nature Communications, 2025, volume 16, issue 1 (DOI: 10.1038/s41467-025-66522-0)
- Three statin molecules cooperate to lock open the RyR1 calcium channel in skeletal muscle cells
- Cryo-electron microscopy at the University of British Columbia captured the interaction at near-atomic resolution
- More than 200 million people worldwide take statins
- Lead author Dr. Steven Molinarolo and senior author Dr. Filip Van Petegem at the University of British Columbia
More than 200 million statin users worldwide now have a molecular explanation for their muscle pain: three drug molecules work together to lock open a calcium channel inside muscle cells, a UBC-led team reports.
The study appears in Nature Communications, 2025; volume 16, issue 1 (DOI: 10.1038/s41467-025-66522-0). It comes from the University of British Columbia with collaborators at the University of Wisconsin-Madison.
What did the team actually see?
Researchers used cryo-electron microscopy at UBC's high-resolution macromolecular facility to image how atorvastatin engages RyR1, the calcium-release receptor that fires during skeletal muscle contraction. The channel should open in short bursts tied to nerve signals. Statins keep it open instead.
The continuous calcium flow dumps ions into the cytoplasm where they do not belong. Over weeks and months, the excess damages muscle fibers. That molecular story matches the clinical pattern: soreness, fatigue, and weakness in many users, and rhabdomyolysis — dangerous muscle breakdown that can trigger kidney failure — in a small share.
Lead author Dr. Steven Molinarolo, a postdoctoral researcher in UBC's department of biochemistry and molecular biology, framed the finding: "We were able to see, almost atom by atom, how statins latch onto this channel. That leak of calcium explains why some patients experience muscle pain or, in extreme cases, life-threatening complications."
How does the three-molecule attack work?
The team centered on atorvastatin, the most-prescribed statin in clinical use today. Three drug molecules cooperate on one RyR1 channel. The first docks while the gate is closed and primes it to swing open. Two more then slot into the same pocket and lock the channel in its open state.
The same pocket accommodates related statins, suggesting the mechanism extends across the drug family rather than a single compound.
Senior author Dr. Filip Van Petegem, professor at UBC's Life Sciences Institute, called the structural map a turning point: "This is the first time we've had a clear picture of how statins activate this channel. It's a big step forward because it gives us a roadmap for designing statins that don't interact with muscle tissue."
Why does this matter for the 200 million users?
Severe injury stays rare, but a sizable share of patients quit statins because of muscle symptoms. Each dropout loses cardiovascular protection that took decades of clinical trials to establish — coverage against heart attack and stroke that lowers mortality at the population level.
A structural roadmap changes the chemistry playbook. Drug designers can now aim at the specific contacts statins make with RyR1, reshaping the molecule to keep the cholesterol-lowering effect while steering clear of the calcium channel. The target is concrete, not speculative.
What's next?
The findings guide drug design rather than replace today's prescriptions. Any reformulated statin must still pass through medicinal chemistry optimization, animal studies, and the standard Phase I–III clinical program. The team confirmed the mechanism on RyR1, the skeletal-muscle isoform; whether RyR2 in the heart behaves the same way is an open question.
For clinicians who write statin prescriptions every day, the takeaway is sharper than before: muscle pain now has a measured molecular source, and drug designers can attack it directly.
via news.ubc.ca (Original)
More from Marcus Bennett
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News editor covering regulation, policy and their impact on general science news at SciBeat.
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