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CO2-dependent opening of an inwardly rectifying K+ channel.

Huckstepp RT, Dale N - Pflugers Arch. (2011)

Bottom Line: This reversal potential was shifted by +61 mV following a tenfold increase in extracellular [K(+)] but was insensitive to variations of extracellular [Cl(-)].We propose that this channel is a member of the Kir family.In addition to this K(+) channel, we found that many of the excised patches also contained a conductance carried via a Cl(-)-selective channel.

View Article: PubMed Central - PubMed

Affiliation: School of Life Sciences, University of Warwick, Coventry, CV4 7AL, UK.

ABSTRACT
CO(2) chemosensing is a vital function for the maintenance of life that helps to control acid-base balance. Most studies have reported that CO(2) is measured via its proxy, pH. Here we report an inwardly rectifying channel, in outside-out excised patches from HeLa cells that was sensitive to modest changes in PCO(2) under conditions of constant extracellular pH. As PCO(2) increased, the open probability of the channel increased. The single-channel currents had a conductance of 6.7 pS and a reversal potential of -70 mV, which lay between the K(+) and Cl(-) equilibrium potentials. This reversal potential was shifted by +61 mV following a tenfold increase in extracellular [K(+)] but was insensitive to variations of extracellular [Cl(-)]. The single-channel conductance increased with extracellular [K(+)]. We propose that this channel is a member of the Kir family. In addition to this K(+) channel, we found that many of the excised patches also contained a conductance carried via a Cl(-)-selective channel. This CO(2)-sensitive Kir channel may hyperpolarize excitable cells and provides a potential mechanism for CO(2)-dependent inhibition during hypercapnia.

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Related in: MedlinePlus

Channel open time distributions recorded at different levels of PCO2. Analysis of raw data from Fig. 1. The solid line is the combined fit of two exponential distributions, each shown separately as grey dashed lines. At each level of PCO2, the fitting of two exponential distributions gave a statistically significantly better fit than a single exponential (P < 0.02, F test). The effects of 55 and 70 mmHg on channel open times are probably underestimated as these were taken from stretches of data early in the application of the elevated PCO2 to minimize the occurrence of multiple-channel openings
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Fig2: Channel open time distributions recorded at different levels of PCO2. Analysis of raw data from Fig. 1. The solid line is the combined fit of two exponential distributions, each shown separately as grey dashed lines. At each level of PCO2, the fitting of two exponential distributions gave a statistically significantly better fit than a single exponential (P < 0.02, F test). The effects of 55 and 70 mmHg on channel open times are probably underestimated as these were taken from stretches of data early in the application of the elevated PCO2 to minimize the occurrence of multiple-channel openings

Mentions: We examined the distribution of channel open times at different levels of PCO2. Under control conditions (PCO2 35 mmHg), this distribution could be fitted by either one or the sum of two exponential distributions. This demonstrated a main open state with a mean open time of 2.1 ± 0.5 ms (n = 5). However in two of these cases, fitting a second distribution with a longer mean time constant gave a statistically significantly better fit (Fig. 2). We noticed that the prevalence of these longer time openings increased at higher levels of PCO2. In one case, it was possible to measure the mean open times at all four levels of PCO2 (Fig. 2; Table 1). We found that while the short and long mean open times did not vary significantly at different levels of PCO2, the amplitude of the distribution with the longer mean open time scaled with PCO2 (Table 1). This analysis suggests that increased levels of CO2 may increase Po by promoting entry into a second open state that has a longer mean open time (measured over all levels of PCO2, 7.0 ± 1.0 ms, n = 3).Fig. 2


CO2-dependent opening of an inwardly rectifying K+ channel.

Huckstepp RT, Dale N - Pflugers Arch. (2011)

Channel open time distributions recorded at different levels of PCO2. Analysis of raw data from Fig. 1. The solid line is the combined fit of two exponential distributions, each shown separately as grey dashed lines. At each level of PCO2, the fitting of two exponential distributions gave a statistically significantly better fit than a single exponential (P < 0.02, F test). The effects of 55 and 70 mmHg on channel open times are probably underestimated as these were taken from stretches of data early in the application of the elevated PCO2 to minimize the occurrence of multiple-channel openings
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3037493&req=5

Fig2: Channel open time distributions recorded at different levels of PCO2. Analysis of raw data from Fig. 1. The solid line is the combined fit of two exponential distributions, each shown separately as grey dashed lines. At each level of PCO2, the fitting of two exponential distributions gave a statistically significantly better fit than a single exponential (P < 0.02, F test). The effects of 55 and 70 mmHg on channel open times are probably underestimated as these were taken from stretches of data early in the application of the elevated PCO2 to minimize the occurrence of multiple-channel openings
Mentions: We examined the distribution of channel open times at different levels of PCO2. Under control conditions (PCO2 35 mmHg), this distribution could be fitted by either one or the sum of two exponential distributions. This demonstrated a main open state with a mean open time of 2.1 ± 0.5 ms (n = 5). However in two of these cases, fitting a second distribution with a longer mean time constant gave a statistically significantly better fit (Fig. 2). We noticed that the prevalence of these longer time openings increased at higher levels of PCO2. In one case, it was possible to measure the mean open times at all four levels of PCO2 (Fig. 2; Table 1). We found that while the short and long mean open times did not vary significantly at different levels of PCO2, the amplitude of the distribution with the longer mean open time scaled with PCO2 (Table 1). This analysis suggests that increased levels of CO2 may increase Po by promoting entry into a second open state that has a longer mean open time (measured over all levels of PCO2, 7.0 ± 1.0 ms, n = 3).Fig. 2

Bottom Line: This reversal potential was shifted by +61 mV following a tenfold increase in extracellular [K(+)] but was insensitive to variations of extracellular [Cl(-)].We propose that this channel is a member of the Kir family.In addition to this K(+) channel, we found that many of the excised patches also contained a conductance carried via a Cl(-)-selective channel.

View Article: PubMed Central - PubMed

Affiliation: School of Life Sciences, University of Warwick, Coventry, CV4 7AL, UK.

ABSTRACT
CO(2) chemosensing is a vital function for the maintenance of life that helps to control acid-base balance. Most studies have reported that CO(2) is measured via its proxy, pH. Here we report an inwardly rectifying channel, in outside-out excised patches from HeLa cells that was sensitive to modest changes in PCO(2) under conditions of constant extracellular pH. As PCO(2) increased, the open probability of the channel increased. The single-channel currents had a conductance of 6.7 pS and a reversal potential of -70 mV, which lay between the K(+) and Cl(-) equilibrium potentials. This reversal potential was shifted by +61 mV following a tenfold increase in extracellular [K(+)] but was insensitive to variations of extracellular [Cl(-)]. The single-channel conductance increased with extracellular [K(+)]. We propose that this channel is a member of the Kir family. In addition to this K(+) channel, we found that many of the excised patches also contained a conductance carried via a Cl(-)-selective channel. This CO(2)-sensitive Kir channel may hyperpolarize excitable cells and provides a potential mechanism for CO(2)-dependent inhibition during hypercapnia.

Show MeSH
Related in: MedlinePlus