A Kv2 inhibitor combination reveals native neuronal conductances consistent with Kv2/KvS heteromers DOI Open Access
Robert G. Stewart, Matthew James Marquis, Sooyeon Jo

et al.

Published: May 8, 2025

Abstract KvS proteins are voltage-gated potassium channel subunits that form functional channels when assembled into heteromers with Kv2.1 (KCNB1) or Kv2.2 (KCNB2). Mammals have 10 subunits: Kv5.1 (KCNF1), Kv6.1 (KCNG1), Kv6.2 (KCNG2), Kv6.3 (KCNG3), Kv6.4 (KCNG4), Kv8.1 (KCNV1), Kv8.2 (KCNV2), Kv9.1 (KCNS1), Kv9.2 (KCNS2), and Kv9.3 (KCNS3). Electrically excitable cells broadly express containing Kv2 most neurons substantial conductance. However, whether contribute to these conductances has not been clear, leaving the physiological roles of poorly understood. Here, we identify two potent inhibitors, used in combination, can distinguish Kv2/KvS Kv2-only channels. We find Kv5, Kv6, Kv8, Kv9-containing resistant Kv2-selective pore-blocker RY785 yet remain sensitive voltage sensor modulator guangxitoxin-1E (GxTX). Using inhibitors mouse superior cervical ganglion neurons, predominantly RY785-sensitive consistent composed entirely subunits. In contrast, RY785-resistant but GxTX-sensitive heteromeric predominate human dorsal root neurons. These results establish an approach pharmacologically from channels, enabling investigation endogenous findings suggest drugs which could modulate electrical activity subsets Kv2-expressing cell types.

Language: Английский

How the Blind Watchmaker messed around with potassium channels DOI
Lawrence Salkoff

The Journal of General Physiology, Journal Year: 2025, Volume and Issue: 157(3)

Published: March 19, 2025

Studies of potassium channel evolution from the Jegla group contribute valuable insights into complexity in electrical signaling and conservation repurposing key molecular components throughout evolutionary history.

Language: Английский

Citations

0
A Kv2 inhibitor combination reveals native neuronal conductances consistent with Kv2/KvS heteromers DOI Open Access
Robert G. Stewart, Matthew James Marquis, Sooyeon Jo

et al.

Published: May 8, 2025

Abstract KvS proteins are voltage-gated potassium channel subunits that form functional channels when assembled into heteromers with Kv2.1 (KCNB1) or Kv2.2 (KCNB2). Mammals have 10 subunits: Kv5.1 (KCNF1), Kv6.1 (KCNG1), Kv6.2 (KCNG2), Kv6.3 (KCNG3), Kv6.4 (KCNG4), Kv8.1 (KCNV1), Kv8.2 (KCNV2), Kv9.1 (KCNS1), Kv9.2 (KCNS2), and Kv9.3 (KCNS3). Electrically excitable cells broadly express containing Kv2 most neurons substantial conductance. However, whether contribute to these conductances has not been clear, leaving the physiological roles of poorly understood. Here, we identify two potent inhibitors, used in combination, can distinguish Kv2/KvS Kv2-only channels. We find Kv5, Kv6, Kv8, Kv9-containing resistant Kv2-selective pore-blocker RY785 yet remain sensitive voltage sensor modulator guangxitoxin-1E (GxTX). Using inhibitors mouse superior cervical ganglion neurons, predominantly RY785-sensitive consistent composed entirely subunits. In contrast, RY785-resistant but GxTX-sensitive heteromeric predominate human dorsal root neurons. These results establish an approach pharmacologically from channels, enabling investigation endogenous findings suggest drugs which could modulate electrical activity subsets Kv2-expressing cell types.

Language: Английский

Citations

0