KChannelDB: Extraction of mutation data from the literature 2005, KChannelDB.
This data was extracted from Medline abstracts and full texts (when available) in an automated manner.
The table below describes the selected point mutation and provides links to other documents. The sentence(s) where the point mutation T58V was found are listed after the table.
The mutated residues are also indicated in the family sequence alignments and hyperlinked to the corresponding mutation pages.
Point mutation T58V in KCNE1_HUMAN
- A further examination of T58V revealed that the voltage-independent component could be diminished or eliminated and the activation could be slowed by administering a preconditioning hyperpolarization pulse (-120 mV for 3 s) rather than the more physiological holding potential (- 80 mV) (Fig. 2 d)
- The V h of the voltage-activated component of this mutant is not significantly left-shifted relative to minK (T58V , 27.7 ± 1.01 mV , n = 10 , versus WT minK , 30.3 ± 3.1 mV , n = 10)
- Recordings are from CHO cells (obtained as in Fig. 1 ) transfected with KvLQT1 cDNA with F57T / T58V minK (scale bar = 2000 pA) (a) ; F57T / L59G minK (scale bar = 3000 pA) (b) ; T58V / L59G minK (scale bar = 12 , 000 pA) (c) ; T58V minK using voltage protocol with either -80 mV holding potential (left trace) or 3-s conditioning pulse to -120 mV (right trace) before each sweep (scale bar = 4500 pA) (d)
- (F57T / L59G , n = 4 ; T58V / L59G , n = 10 ; F57T / T58V , n = 7 ; and T58V , n = 10.) We also introduced threonines into T58V minK at positions 55 and 61 , one turn N- or C-terminal to residue 58 , respectively
- c , G55T / T58V minK representing substitution of threonine one turn up from the central residue in minK
- d , I61T / T58V minK representing substitution of threonine one turn down from the central residue in minK
- (T58V / G55T , n = 9 ; T58V / I61T , n = 10 ; A69T , n = 5 ; and L75T , n = 4.) (image) View larger version (34K): [in this window] [in a new window] Fig. 4
- The substitution of isoleucine produced a voltage-independent constitutive component that could be decreased by prolonged hyperpolarizations in a manner that is similar to the current seen with the T58V substitution
- a , T58V minK
- However , the deactivation kinetics of T58V minK , T58I minK and T58C minK , and T71F / G73L KCNE3 could not be fit to a monoexponential time course
- The V h of the voltage-dependent component of these minK mutants was not left-shifted to an extent that would account for the constitutive current we observed (T58VminK V h = 27.7 ± 1.07 (n = 10) , T58I minK V h = 26.7 ± 1.07 (n = 4) , T58C minK V h = -8.5 mV ± 1.5 (n = 13) , T71F / G73L KCNE3 -14.93 ± 1.4 mV (n = 7) versus KvLQT1 alone , V h = -15.2 ± 0.3 mV (n = 10) , which shows no such prepulse dependence) and thus cannot be explained merely by a hyperpolarizing shift in activation gating
- T58V minK , T58I minK , and T58C minK appear only to be able to trap partially the channel in this state and only so when the channel assumes the open state driven by the electric field across the membrane during depolarization
- T58V minK exhibits a 'conditional' open state analogous to the voltage-independent open state of KCNE3
- Our results suggest that T58V is an intermediate phenotype between minK- and KCNE3-like gating , and that although a transition may exist between the voltage-independent state and the population of voltage-dependent gating channels , this may be too slow to observe experimentally
F.Horn (kchanneldbcmbi.ru.nl), 17-Aug-2005