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Characteristics of K(+) Outward Currents in the Cochlear Outer Hair Cells of Circling Mice within the First Postnatal Week.

Ahn JW, Kang SW, Ahn SC - Korean J. Physiol. Pharmacol. (2015)

Bottom Line: Similar slow rising K(+) currents were observed in both genotypes, but their biophysical and pharmacological properties were quite different.The K(+) current of homozygous (cir/cir) mice was more sensitive to TEA in the 1 to 10 mM range, while the 4-AP sensitivities were not different between the two genotypes.Removal of external Ca(2+) did not affect the K(+) currents in either genotype, indicating that the higher sensitivity of K(+) current to TEA in the homozygous (cir/cir) mice was not due to an early expression of Ca(2+) activated K(+) channels.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology, College of Medicine, Dankook University, Cheonan 330-714, Korea.

ABSTRACT
K(+) outward currents in the outer hair cells (OHCs) of circling mice (homozygous (cir/cir) mice), an animal model for human deafness (DFNB6 type), were investigated using a whole cell patch clamp technique. Littermate heterozygous (+/cir) mice of the same age (postnatal day (P) 0 -P6) were used as controls. Similar slow rising K(+) currents were observed in both genotypes, but their biophysical and pharmacological properties were quite different. The values of Vhalf for activation were significantly different in the heterozygous (+/cir) and homozygous (cir/cir) mice (-8.1±2.2 mV, heterozygous (+/cir) mice (n=7) and -17.2±4.2 mV, homozygous (cir/cir) mice (n=5)). The inactivation curve was expressed by a single first order Boltzmann equation in the homozygous (cir/cir) mice, while it was expressed by a sum of two first order Boltzmann equations in the heterozygous (+/cir) mice. The K(+) current of homozygous (cir/cir) mice was more sensitive to TEA in the 1 to 10 mM range, while the 4-AP sensitivities were not different between the two genotypes. Removal of external Ca(2+) did not affect the K(+) currents in either genotype, indicating that the higher sensitivity of K(+) current to TEA in the homozygous (cir/cir) mice was not due to an early expression of Ca(2+) activated K(+) channels. Our results suggest that the K(+) outward current of developing homozygous (cir/cir) mice OHCs is different in both biophysical and pharmacological aspects than that of heterozygous (+/cir) mice.

No MeSH data available.


Related in: MedlinePlus

Whole cell K+ outward currents of P0-P6 mice OHCs. Current traces recorded from P5 heterozygous (+/cir) and P3 homozygous (cir/cir) mouse are shown in A and B. Currents were elicited by depolarizing voltage steps from -100 mV to 40 mV with 10 mV increment (holding potential: -60 mV). Voltage protocol is shown above the current traces. Current density-voltage curves are shown in C (filled circle: heterozygous (+/cir) mouse, hollow circle: homozygous (cir/cir) mouse). Cell capacitance changes from P0 to P6 are shown in D (filled circle: heterozygous (+/cir) mouse, hollow circle: homozygous (cir/cir) mouse). Cell capacitances are 5.09±0.4 (P2, n=13), 5.7±0.3 (P3, n=15), 5.7±0.3 (P4, n=15), 5.3±0.2 (P5, n=16), and 5.3±0.3 (P6, n=12) in heterozygous (+/cir) mice. They are 5.9±0.3 (P1, n=12), 5.9±0.2 (P3, n=21), 5.5±0.2 (P4, n=26), 5.6±0.1 (P5, n=30), and 5.9±0.1 (P6, n=29) in homozygous (cir/cir) mice.
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Figure 1: Whole cell K+ outward currents of P0-P6 mice OHCs. Current traces recorded from P5 heterozygous (+/cir) and P3 homozygous (cir/cir) mouse are shown in A and B. Currents were elicited by depolarizing voltage steps from -100 mV to 40 mV with 10 mV increment (holding potential: -60 mV). Voltage protocol is shown above the current traces. Current density-voltage curves are shown in C (filled circle: heterozygous (+/cir) mouse, hollow circle: homozygous (cir/cir) mouse). Cell capacitance changes from P0 to P6 are shown in D (filled circle: heterozygous (+/cir) mouse, hollow circle: homozygous (cir/cir) mouse). Cell capacitances are 5.09±0.4 (P2, n=13), 5.7±0.3 (P3, n=15), 5.7±0.3 (P4, n=15), 5.3±0.2 (P5, n=16), and 5.3±0.3 (P6, n=12) in heterozygous (+/cir) mice. They are 5.9±0.3 (P1, n=12), 5.9±0.2 (P3, n=21), 5.5±0.2 (P4, n=26), 5.6±0.1 (P5, n=30), and 5.9±0.1 (P6, n=29) in homozygous (cir/cir) mice.

Mentions: Typical examples of K+ currents recorded from neonatal OHCs of heterozygous (+/cir) and homozygous (cir/cir) mice are shown in Figs. 1A and 1B, respectively. Depolarizing voltage steps from -100 mV to 40 mV (holding potential: -60 mV) evoked slowly inactivating outward K+ currents in the OHCs of both genotypes, which were similar to that reported previously (a delayed rectifier-type K+ current, IK,neo [1,4], for neonatal cells). Almost no inward currents were elicited by the hyperpolarizing voltage steps from -60 mV to -100 mV in both genotypes (Figs. 1A and 1B). Using the current amplitudes measured at the end of voltage steps (200 ms) and cell capacitance measured from current transients in response to 2 mV step pulses, current densities were calculated for analysis. In heterozygous (+/cir) and homozygous (cir/cir) mice, cell capacitance was 5.5±0.1 pF (n=66) and 5.7±0.1 pF (n=118). The two values were not significantly different. The developmental changes were not significantly different either in two groups (Fig. 1D). The current densities measured at 40 mV were 227.1±18.9 pA/pF (n=16) in heterozygous (+/cir) mice and 238.9±14.3 pA/pF (n=22) in homozygous (cir/cir) mice (Fig. 1C). The two values were not different significantly. Reversal potentials, determined by applying a conditioning pulse to 0 mV, followed by a series of test pulses from -120 mV to -50 mV with a 10 mV increment (data not shown), were -60.5±1.3 mV in the heterozygous (+/cir) mice (n=7) and -57.8±0.9 mV in the homozygous (cir/cir) mice (n=5). The two values were not significantly different.


Characteristics of K(+) Outward Currents in the Cochlear Outer Hair Cells of Circling Mice within the First Postnatal Week.

Ahn JW, Kang SW, Ahn SC - Korean J. Physiol. Pharmacol. (2015)

Whole cell K+ outward currents of P0-P6 mice OHCs. Current traces recorded from P5 heterozygous (+/cir) and P3 homozygous (cir/cir) mouse are shown in A and B. Currents were elicited by depolarizing voltage steps from -100 mV to 40 mV with 10 mV increment (holding potential: -60 mV). Voltage protocol is shown above the current traces. Current density-voltage curves are shown in C (filled circle: heterozygous (+/cir) mouse, hollow circle: homozygous (cir/cir) mouse). Cell capacitance changes from P0 to P6 are shown in D (filled circle: heterozygous (+/cir) mouse, hollow circle: homozygous (cir/cir) mouse). Cell capacitances are 5.09±0.4 (P2, n=13), 5.7±0.3 (P3, n=15), 5.7±0.3 (P4, n=15), 5.3±0.2 (P5, n=16), and 5.3±0.3 (P6, n=12) in heterozygous (+/cir) mice. They are 5.9±0.3 (P1, n=12), 5.9±0.2 (P3, n=21), 5.5±0.2 (P4, n=26), 5.6±0.1 (P5, n=30), and 5.9±0.1 (P6, n=29) in homozygous (cir/cir) mice.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4499651&req=5

Figure 1: Whole cell K+ outward currents of P0-P6 mice OHCs. Current traces recorded from P5 heterozygous (+/cir) and P3 homozygous (cir/cir) mouse are shown in A and B. Currents were elicited by depolarizing voltage steps from -100 mV to 40 mV with 10 mV increment (holding potential: -60 mV). Voltage protocol is shown above the current traces. Current density-voltage curves are shown in C (filled circle: heterozygous (+/cir) mouse, hollow circle: homozygous (cir/cir) mouse). Cell capacitance changes from P0 to P6 are shown in D (filled circle: heterozygous (+/cir) mouse, hollow circle: homozygous (cir/cir) mouse). Cell capacitances are 5.09±0.4 (P2, n=13), 5.7±0.3 (P3, n=15), 5.7±0.3 (P4, n=15), 5.3±0.2 (P5, n=16), and 5.3±0.3 (P6, n=12) in heterozygous (+/cir) mice. They are 5.9±0.3 (P1, n=12), 5.9±0.2 (P3, n=21), 5.5±0.2 (P4, n=26), 5.6±0.1 (P5, n=30), and 5.9±0.1 (P6, n=29) in homozygous (cir/cir) mice.
Mentions: Typical examples of K+ currents recorded from neonatal OHCs of heterozygous (+/cir) and homozygous (cir/cir) mice are shown in Figs. 1A and 1B, respectively. Depolarizing voltage steps from -100 mV to 40 mV (holding potential: -60 mV) evoked slowly inactivating outward K+ currents in the OHCs of both genotypes, which were similar to that reported previously (a delayed rectifier-type K+ current, IK,neo [1,4], for neonatal cells). Almost no inward currents were elicited by the hyperpolarizing voltage steps from -60 mV to -100 mV in both genotypes (Figs. 1A and 1B). Using the current amplitudes measured at the end of voltage steps (200 ms) and cell capacitance measured from current transients in response to 2 mV step pulses, current densities were calculated for analysis. In heterozygous (+/cir) and homozygous (cir/cir) mice, cell capacitance was 5.5±0.1 pF (n=66) and 5.7±0.1 pF (n=118). The two values were not significantly different. The developmental changes were not significantly different either in two groups (Fig. 1D). The current densities measured at 40 mV were 227.1±18.9 pA/pF (n=16) in heterozygous (+/cir) mice and 238.9±14.3 pA/pF (n=22) in homozygous (cir/cir) mice (Fig. 1C). The two values were not different significantly. Reversal potentials, determined by applying a conditioning pulse to 0 mV, followed by a series of test pulses from -120 mV to -50 mV with a 10 mV increment (data not shown), were -60.5±1.3 mV in the heterozygous (+/cir) mice (n=7) and -57.8±0.9 mV in the homozygous (cir/cir) mice (n=5). The two values were not significantly different.

Bottom Line: Similar slow rising K(+) currents were observed in both genotypes, but their biophysical and pharmacological properties were quite different.The K(+) current of homozygous (cir/cir) mice was more sensitive to TEA in the 1 to 10 mM range, while the 4-AP sensitivities were not different between the two genotypes.Removal of external Ca(2+) did not affect the K(+) currents in either genotype, indicating that the higher sensitivity of K(+) current to TEA in the homozygous (cir/cir) mice was not due to an early expression of Ca(2+) activated K(+) channels.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology, College of Medicine, Dankook University, Cheonan 330-714, Korea.

ABSTRACT
K(+) outward currents in the outer hair cells (OHCs) of circling mice (homozygous (cir/cir) mice), an animal model for human deafness (DFNB6 type), were investigated using a whole cell patch clamp technique. Littermate heterozygous (+/cir) mice of the same age (postnatal day (P) 0 -P6) were used as controls. Similar slow rising K(+) currents were observed in both genotypes, but their biophysical and pharmacological properties were quite different. The values of Vhalf for activation were significantly different in the heterozygous (+/cir) and homozygous (cir/cir) mice (-8.1±2.2 mV, heterozygous (+/cir) mice (n=7) and -17.2±4.2 mV, homozygous (cir/cir) mice (n=5)). The inactivation curve was expressed by a single first order Boltzmann equation in the homozygous (cir/cir) mice, while it was expressed by a sum of two first order Boltzmann equations in the heterozygous (+/cir) mice. The K(+) current of homozygous (cir/cir) mice was more sensitive to TEA in the 1 to 10 mM range, while the 4-AP sensitivities were not different between the two genotypes. Removal of external Ca(2+) did not affect the K(+) currents in either genotype, indicating that the higher sensitivity of K(+) current to TEA in the homozygous (cir/cir) mice was not due to an early expression of Ca(2+) activated K(+) channels. Our results suggest that the K(+) outward current of developing homozygous (cir/cir) mice OHCs is different in both biophysical and pharmacological aspects than that of heterozygous (+/cir) mice.

No MeSH data available.


Related in: MedlinePlus