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• W2022309429 endingPage "2994" @default.
• W2022309429 startingPage "2982" @default.
• W2022309429 abstract "At low Popen(V) Shaker exhibits pronounced stretch-activation. Possible explanations for Shaker’s sensitivity to tension include 1) Shaker channels are sufficiently distensible that stretch produces novel channel states and 2) Shaker channels expand in the plane of the membrane during voltage gating. For channels expressed in oocytes, we compared effects of patch stretch on Shaker and mutants that retain their voltage-gating ability but activate sluggishly because all or most of the S3–S4 linker has been deleted. Deletants had 10, 5, or 0 amino acid (aa) linkers, whereas wild-type is 31 aa . In deletants, though activation is exceptionally slow, slow inactivation is exceptionally quick; the resulting kinetic match was a bonus that allowed effects of stretch to be followed simultaneously in both processes. With the intact linker, an ∼3 orders of magnitude mismatch in the two processes makes this impracticable. Standard stretch stimuli increased the rates and extent of activation by about the same degree in wild type and deletants, with effects especially pronounced near the foot of G(V). In deletants (where slow inactivation is strongly coupled to activation) stretch also accelerated slow inactivation. Maximum conductances were unaffected by stretch in all variants. In ramp clamp dose experiments, near-lytic patch stretch acted, for all variants, like a ∼10 mV hyperpolarizing shift. These results suggested that, whether basal rates were high (wild type) or low (deletants), stretch acted by facilitating voltage-dependent activation. Channel activity was therefore simulated with/without “tension,” tension being simulated via rate changes at voltage-dependent closed-closed transitions that might involve in-plane expansion (explanation 2). Simulated ΔPopen arising from ∼2 kT of “mechanical gating energy” mimicked experimental effects seen with comfortably sub-lytic stretch." @default.
• W2022309429 created "2016-06-24" @default.
• W2022309429 creator A5070995015 @default.
• W2022309429 creator A5090888866 @default.
• W2022309429 date "2002-06-01" @default.
• W2022309429 modified "2023-10-16" @default.
• W2022309429 title "Membrane Stretch Accelerates Activation and Slow Inactivation in Shaker Channels with S3–S4 Linker Deletions" @default.
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• W2022309429 doi "https://doi.org/10.1016/s0006-3495(02)75639-7" @default.
• W2022309429 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/1302086" @default.
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