Tags

Type your tag names separated by a space and hit enter

Alterations in outward K(+) currents on removal of external Ca(2+) in human atrial myocytes.
Biochem Biophys Res Commun. 2000 Jun 24; 273(1):10-6.BB

Abstract

External divalent cations are known to play an important role in the function of voltage-gated ion channels. The purpose of this study was to examine the sensitivity of the voltage-gated K(+) currents of human atrial myocytes to external Ca(2+) ions. Myocytes were isolated by collagenase digestion of atrial appendages taken from patients undergoing coronary artery-bypass surgery. Currents were recorded from single isolated myocytes at 37 degrees C using the whole-cell patch-clamp technique. With 0.5 mM external Ca(2+), voltage pulses positive to -20 mV (holding potential = -60 mV) activated outward currents which very rapidly reached a peak (I(peak)) and subsequently inactivated (tau = 7.5 +/- 0.7 msec at +60 mV) to a sustained level, demonstrating the contribution of both rapidly inactivating transient (I(to1)) and non-inactivating sustained (I(so)) outward currents. The I(to1) component of I(peak), but not I(so), showed voltage-dependent inactivation using 100 msec prepulses (V(1/2) = -35.2 +/- 0.5 mV). The K(+) channel blocker, 4-aminopyridine (4-AP, 2 mM), inhibited I(to1) by approximately 76% and reduced I(so) by approximately 33%. Removal of external Ca(2+) had several effects: (i) I(peak) was reduced in a manner consistent with an approximately 13 mV shift to negative voltages in the voltage-dependent inactivation of I(to1). (ii) I(so) was increased over the entire voltage range and this was associated with an increase in a non-inactivating 4-AP-sensitive current. (iii) In 79% cells (11/14), a slowly inactivating component was revealed such that the time-dependent inactivation was described by a double exponential time course (tau(1) = 7.0 +/- 0.7, tau(2) = 90 +/- 21 msec at +60 mV) with no effect on the fast time constant. Removal of external Ca(2+) was associated with an additional component to the voltage-dependent inactivation of I(peak) and I(so) (V(1/2) = -20.5 +/- 1.5 mV). The slowly inactivating component was seen only in the absence of external Ca(2+) ions and was insensitive to 4-AP (2 mM). Experiments with Cs(+)-rich pipette solutions suggested that the Ca(2+)-sensitive currents were carried predominantly by K(+) ions. External Ca(2+) ions are important to voltage-gated K(+) channel function in human atrial myocytes and removal of external Ca(2+) ions affects I(to1) and 4-AP-sensitive I(so) in distinct ways.

Links

Publisher Full Text

Authors+Show Affiliations

Bertaso F
Cell Signalling Group, King's College London, London, United Kingdom.
Hendry BM
No affiliation info available
Donohoe P
No affiliation info available
James AF
No affiliation info available

MeSH

4-AminopyridineCalciumCalcium Channel BlockersCations, DivalentCells, CulturedCesiumElectric ConductivityHeart AtriaHumansIon Channel GatingKineticsMembrane PotentialsPatch-Clamp TechniquesPotassiumPotassium Channel BlockersPotassium ChannelsTemperatureVerapamil

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

10873555

Citation

Bertaso, F, et al. "Alterations in Outward K(+) Currents On Removal of External Ca(2+) in Human Atrial Myocytes." Biochemical and Biophysical Research Communications, vol. 273, no. 1, 2000, pp. 10-6.
Bertaso F, Hendry BM, Donohoe P, et al. Alterations in outward K(+) currents on removal of external Ca(2+) in human atrial myocytes. Biochem Biophys Res Commun. 2000;273(1):10-6.
Bertaso, F., Hendry, B. M., Donohoe, P., & James, A. F. (2000). Alterations in outward K(+) currents on removal of external Ca(2+) in human atrial myocytes. Biochemical and Biophysical Research Communications, 273(1), 10-6.
Bertaso F, et al. Alterations in Outward K(+) Currents On Removal of External Ca(2+) in Human Atrial Myocytes. Biochem Biophys Res Commun. 2000 Jun 24;273(1):10-6. PubMed PMID: 10873555.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Alterations in outward K(+) currents on removal of external Ca(2+) in human atrial myocytes. AU - Bertaso,F, AU - Hendry,B M, AU - Donohoe,P, AU - James,A F, PY - 2000/6/30/pubmed PY - 2000/6/30/medline PY - 2000/6/30/entrez SP - 10 EP - 6 JF - Biochemical and biophysical research communications JO - Biochem Biophys Res Commun VL - 273 IS - 1 N2 - External divalent cations are known to play an important role in the function of voltage-gated ion channels. The purpose of this study was to examine the sensitivity of the voltage-gated K(+) currents of human atrial myocytes to external Ca(2+) ions. Myocytes were isolated by collagenase digestion of atrial appendages taken from patients undergoing coronary artery-bypass surgery. Currents were recorded from single isolated myocytes at 37 degrees C using the whole-cell patch-clamp technique. With 0.5 mM external Ca(2+), voltage pulses positive to -20 mV (holding potential = -60 mV) activated outward currents which very rapidly reached a peak (I(peak)) and subsequently inactivated (tau = 7.5 +/- 0.7 msec at +60 mV) to a sustained level, demonstrating the contribution of both rapidly inactivating transient (I(to1)) and non-inactivating sustained (I(so)) outward currents. The I(to1) component of I(peak), but not I(so), showed voltage-dependent inactivation using 100 msec prepulses (V(1/2) = -35.2 +/- 0.5 mV). The K(+) channel blocker, 4-aminopyridine (4-AP, 2 mM), inhibited I(to1) by approximately 76% and reduced I(so) by approximately 33%. Removal of external Ca(2+) had several effects: (i) I(peak) was reduced in a manner consistent with an approximately 13 mV shift to negative voltages in the voltage-dependent inactivation of I(to1). (ii) I(so) was increased over the entire voltage range and this was associated with an increase in a non-inactivating 4-AP-sensitive current. (iii) In 79% cells (11/14), a slowly inactivating component was revealed such that the time-dependent inactivation was described by a double exponential time course (tau(1) = 7.0 +/- 0.7, tau(2) = 90 +/- 21 msec at +60 mV) with no effect on the fast time constant. Removal of external Ca(2+) was associated with an additional component to the voltage-dependent inactivation of I(peak) and I(so) (V(1/2) = -20.5 +/- 1.5 mV). The slowly inactivating component was seen only in the absence of external Ca(2+) ions and was insensitive to 4-AP (2 mM). Experiments with Cs(+)-rich pipette solutions suggested that the Ca(2+)-sensitive currents were carried predominantly by K(+) ions. External Ca(2+) ions are important to voltage-gated K(+) channel function in human atrial myocytes and removal of external Ca(2+) ions affects I(to1) and 4-AP-sensitive I(so) in distinct ways. SN - 0006-291X UR - https://www.unboundmedicine.com/medline/citation/10873555/Alterations_in_outward_K_+__currents_on_removal_of_external_Ca_2+__in_human_atrial_myocytes_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-291X(00)92886-9 DB - PRIME DP - Unbound Medicine ER -