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This Article Full Text Full Text (PDF) All Versions of this Article: 548/3/691    most recent 2003.039198v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Zhang, S. Articles by Fedida, D. Search for Related Content PubMed PubMed Citation Articles by Zhang, S. Articles by Fedida, D.

Modulation of human ether-à-go-go-related K⁺ (HERG) channel inactivation by Cs⁺ and K⁺

Shetuan Zhang, Steven J. Kehl and David Fedida

Unlike many other native and cloned K⁺ channels, human ether-à-go-go-related K⁺ (HERG) channels show significant Cs⁺ permeability with a P_Cs/P_K (the permeability of Cs⁺ relative to that of K⁺) of 0.36 ± 0.03 (n = 10). Here, we find that raising the concentration of external Cs⁺ (Cs) dramatically slows HERG channel inactivation without affecting activation. Replacement of 5 mM K by 135 mM Cs increased both inactivation and recovery time constants and shifted the mid-point of the steady-state inactivation curve by 25 mV in the depolarized direction (n = 6, P < 0.01). Raising [Cs⁺]_o also modulated the voltage sensitivity of inactivation gating. With 130 mM Cs and 135 mM NMDG, the inactivation time constant decreased e-fold per 47.5 ± 1.1 mV (n = 5), and when 20 mM Cs⁺ was added to the bath solution, the inactivation time constant decreased e-fold per 20.6 ± 1.3 mV (n = 5, P < 0.01). A quantitative analysis suggests that Cs binds to a site in the pore that is influenced by the transmembrane electrical field, so that Cs-induced slowing of HERG inactivation is less prominent at strong depolarizations. K has effects that are similar to Cs and their effects were additive, suggesting Cs and K may share a common mechanism of action. The strong effects of Cs⁺ on inactivation but not on activation highlight the importance of ion and channel interactions during the onset of inactivation in the HERG channel.

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