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Rapid induction of P/C-type inactivation is the mechanism for acid-induced K+ current inhibition.

ABSTRACT: Extracellular acidification is known to decrease the conductance of many voltage-gated potassium channels. In the present study, we investigated the mechanism of H(+)(o)-induced current inhibition by taking advantage of Na(+) permeation through inactivated channels. In hKv1.5, H(+)(o) inhibited open-state Na(+) current with a similar potency to K(+) current, but had little effect on the amplitude of inactivated-state Na(+) current. In support of inactivation as the mechanism for the current reduction, Na(+) current through noninactivating hKv1.5-R487V channels was not affected by [H(+)(o)]. At pH 6.4, channels were maximally inactivated as soon as sufficient time was given to allow activation, which suggested two possibilities for the mechanism of action of H(+)(o). These were that inactivation of channels in early closed states occurred while hyperpolarized during exposure to acid pH (closed-state inactivation) and/or inactivation from the open state was greatly accelerated at low pH. The absence of outward Na(+) currents but the maintained presence of slow Na(+) tail currents, combined with changes in the Na(+) tail current time course at pH 6.4, led us to favor the hypothesis that a reduction in the activation energy for the inactivation transition from the open state underlies the inhibition of hKv1.5 Na(+) current at low pH.

SUBMITTER: Zhang S

PROVIDER: S-EPMC2217332 | biostudies-literature | 2003 Mar

REPOSITORIES: biostudies-literature

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Rapid induction of P/C-type inactivation is the mechanism for acid-induced K+ current inhibition.

Zhang Shetuan S Kurata Harley T HT Kehl Steven J SJ Fedida David D

The Journal of general physiology 20030301 3

Extracellular acidification is known to decrease the conductance of many voltage-gated potassium channels. In the present study, we investigated the mechanism of H(+)(o)-induced current inhibition by taking advantage of Na(+) permeation through inactivated channels. In hKv1.5, H(+)(o) inhibited open-state Na(+) current with a similar potency to K(+) current, but had little effect on the amplitude of inactivated-state Na(+) current. In support of inactivation as the mechanism for the current redu ...[more]

PMID: 12601085

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Project description:Rapid sequence induction and intubation (RSII) is a technique commonly used to resist regurgitation of gastric contents and protect the airway. A modification of this technique is implemented in certain clinical circumstances. However, there is currently no standard definition for a modified RSII. Therefore, we surveyed clinicians at academic centers across the United States to establish a working definition of a modified RSII as well as the clinical scenarios in which it is being used.A survey was created that queried the use and definition of modified RSII, and validated with test respondents. We then mailed the survey to all 131 anesthesia residency training programs across the United States. Logistic regression models were created to estimate the percentage of affirmative responses among respondents that performed modified RSII procedures and answered survey items in a consistent manner. Similar quantities were calculated by physician status (resident and attending).Four hundred ninety surveys were received from 58 institutions (44% institution response rate); 93% of respondents reported using a modified RSII, and of those 85% consistently completed the survey instrument. A majority of respondents (71%, CI: 63%-77%) reported administering oxygen before anesthesia induction, applying cricoid pressure, and attempting to ventilate the lungs via a facemask before securing the airway. Respondents noted that they would use a modified RSII procedure if the patient were either moderately or morbidly obese (each ?59%, 53%-64%), had a history but no current symptoms of gastroesophageal reflux disease (52%, 46%-57%), had a hiatal hernia (42%, 36%-48%) or were a trauma patient who had been NPO for at least 8 h (39%, 33%-45%). Similar RSII results were obtained when repeating the analysis on the subset that did not enforce the consistency requirements.Based on our survey we have established three defining features of a modified RSII: (1) oxygen administration before induction; (2) the use of cricoid pressure; and (3) an attempt to ventilate the patient's lungs before securing the airway. Although this definition seems intuitively obvious, no previous work has tested whether it is commonly accepted.

Dataset Information

Rapid induction of P/C-type inactivation is the mechanism for acid-induced K+ current inhibition.

Publications

Rapid induction of P/C-type inactivation is the mechanism for acid-induced K+ current inhibition.

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