Antonios Pantazis lab

"Hearts and Minds" achievement unlocked! Our lab is now receiving simultaneous funding by the Swedish Heart-Lung Foundation ❤️ and the Swedish Brain Foundation 🧠!
(been waiting all year to be able to say this)

2nd #WSCC26 will take place in Grindelwald (Switzerland) 🚠 from 4th to 6th of February, 2026.

🌍 Join @lampertlab.bsky.social , @antoniospantazis.bsky.social, @khannalabuf.bsky.social, and others.

💡 Submit abstracts by the 26th of September, 2025:
lnkd.in/eDhPUVKd

💻 More info:
lnkd.in/eJw9pfMz

Very excited to share our most recent work on using de novo design to custom engineer a small peptide that can restore proper sodium channel function in disease … to be able to “write” proteins to do whatever we want them to do, is just remarkable …

SOX2 and NR2F1 coordinate the gene expression program of the early postnatal visual thalamus Summary: The transcriptional regulators SOX2 and NR2F1 drive the development of the visual thalamus. Mutations in these genes cause visual impairment in humans.

SOX2 and NR2F1 cooperate
to make #neurons in the #Thalamus
for visual input from the #retina

#DevBio

journals.biologists.com/bio/article/...
‪
@biologyopen.bsky.social

In collab w Sara Mercurio and Silvia Nicolis @btbsunimib.bsky.social

Driven by Linda Serra and @annanordin.bsky.social

Glass of tequila and a play through of Pet Sounds. RIP Brian Wilson, on a very Californian evening in southern Sweden.

Congratulations! Also, great still! I think that's my favorite Black Books episode :-)

A rich conformational palette underlies human CaV2.1-channel availability Nature Communications - CaV2.1 channels are critical for neuronal communication. Here, authors showed they undergo electrically-evoked molecular movements which (1) eventually trigger...

Out now at Nat Comm: "A rich conformational palette 🎨 underlies human CaV2.1-channel availability"
1. VSD-I activation triggers transmitter release
2. VSD-I conversion causes VDI & contributes to plasticity
3. CaV2.1 channels have several conformations at Vrest
#neuroskyence #CACNA1A
rdcu.be/ei0Tm

An immensely interesting seminar with plot twists is going to take place next Tuesday! 🕵

⚡ Join the exciting talk of @antoniospantazis.bsky.social titled "Even a single carbon atom matters: deadly and unexpected consequences of a Nav1.5 variant". 🫀

to connect: lnkd.in/evCC__x7

It will be turbulent in the next worldwide sodium channel seminar: @antoniospantazis.bsky.social will explain why "Even a single carbon atom matters: deadly and unexpected consequences of a Nav1.5 variant" Tuesday April 29th. Visit www.sodiumchannelseminars.org for link and infos. #sodiumchannel

11/11 Congrats to S. Pozzi for spectacular COVG experiments & her 1st 1st-author paper! Our gratitude goes to patients & their doctors, our clinical collaborators at Sahlgrenska for reaching out & doing clinical characterization, and team-HPLarsson for pharmacology expts. And thank you for reading ❤️

10/11 So, just like MK Shyamalan stories, we end ours with an open question on the mechanism of arrhythmogenesis. But unlike MKS, we are following up! We are doing more molecular studies (VCF, slow inactivation) and we expect mutagenized iPSCs any day now. We are also procuring patient stem cells.

9/11 TWIST #3: I1333V abolishes the Nav1.5 response to cAMP! cAMP normally produces Nav1.5 upregulation, due to trafficking of reserve channels or loss of slow inactivation. We don't know whether mutant channels do not get upregulated, or if they are "pre-upregulated". Either way, interesting stuff!

8/11 One more piece for this puzzle: the arrhythmias are exercise induced. During exercise, the heart is under adrenergic stimulation. When we tried to mimic how Nav1.5 responds to this condition (by perfusing membrane-permeable cAMP), we found that... 🥁🥁🥁

Left: ToR-ORd model predicts earlier and stronger AP onset; middle: this is due to elevated Na influx through NaV1.5; right: this causes increased NCX outward current. The latter means that NCX is operating in "reverse mode", extruding Na and importing Ca.

7/11 So if I1333V does not affect AP morphology, how does it cause arrhythmia? The model also predicted ⬆️ Na influx at AP onset and ⬆️ Ca import by the Na/Ca exchanger (NCX). We propose that this causes ⬆️Ca release and then Ca overload, similar to canonical CPVT mutations.

Action-potential clamp shows no significant increase in late current

To ToR-ORd model of human ventricular myocytes predicts no significant increase in AP duration.

6/11 AP-clamp experiments also show insignificant increase in late current. And the "ToR-ORd" model predicts no AP prolongation. The "window current" increases only towards negative voltages. Increased Nav1.5 availability only happens at the very end of the AP, where it can have no effect.

I1333V facilitates voltage-dependent opening...

...but leaves fast inactivation intact.

5/11 TWIST #2: in Nav1.5, opening is also augmented, but fast inactivation is left intact. We can learn much from variant effects on paralogues, but not everything: experiments are still essential! This likely explains why LQT is only a minor effect in the patients. We looked into AP effects next.

(A) Nav membrane topology;(B) channel top & side views; (C) zoom-in on mutation site. * denotes ablated methyl group; (D) sequence homology

4/11 The mutation (I1333V) ablates just one methyl group in a protein of over 2000 residues! But its position is conserved in all Na-channel isoforms. When in 💪Nav1.4, this mutation causes #paralysis; in 🧠Nav1.6, #epilepsy. In both cases, opening was augmented while fast inactivation was impaired.

3/11 SCN5A can cause several 🫀disorders
-LQT: underrepresented & should improve with exercise
-BrS: not evident
-MEPPC: causes cardiomyopathy (not evident)
Ie patients had the "wrong variant" for their disease, or the "wrong disease" for their variant. Could this be a new type of cardiac arrhythmia?

Family pedigrees and representative ECGs

2/11 We discovered 19 people with familial exercise-induced arrhythmia. This pointed to #CPVT, caused by mutations in Ca-handling genes. Except their Ca-genes were OK! Tragically, this led to misdiagnosis & preventable deaths. TWIST #1: all had a mutation in SCN5A (Nav1.5), the 🫀 sodium channel.

Clinical and electrophysiological characterization of a SCN5A gain-of-function mutation associated with CPVT-like arrhythmia The present study aimed to characterize the SCN5A variant I1333V, found in five families with a history of suspected catecholaminergic polymorphic ventricular tachycardia (CPVT). SCN5A encodes the por...

New paper blue-torial! On the surface, it's a new ⚡Nav1.5 #channelopathy causing 🫀 familial cardiac #arrhythmia. But our story has enough plot twists to rival MK Shyamalan!
www.jmcc-online.com/article/S002...
🧵 1/11

New grant for recruiting researchers active outside Europe In mid-April, the Swedish Research Council will issue a call for grants of 2 million SEK to enable Swedish higher education institutions and other research organisations to recruit prominent researche...

Spread the news! Grants available to recruit scientists from outside of Europe to Sweden 🇸🇪 🧠
Please re-post.