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Properties of a time-dependent potassium current in pig atrium: evidence for a role of kv1.5 in repolarization.
J Pharmacol Exp Ther. 2006 Nov; 319(2):898-906.JP

Abstract

Cardiac electrical activity is modulated by potassium currents. Pigs have been used for antiarrhythmic drug testing, but only sparse data exist regarding porcine atrial ionic electrophysiology. Here, we used electrophysiological, molecular, and pharmacological tools to characterize a prominent porcine outward K(+) current (I(K,PO)) in atrial cardiomyocytes isolated from adult pigs. I(K,PO) activated rapidly (time to peak at +60 mV; 2.1 +/- 0.2 ms), inactivated slowly (tau(f) = 45 +/- 10; tau(s) = 215 +/- 28 ms), and showed very slow recovery (tau(f) = 1.54 +/- 0.73 s; tau(s) = 7.91 +/- 1.78 s; n = 9; 36 degrees C). Activation and inactivation were voltage-dependent, and current properties were consistent with predominant K(+) conductance. Neurotoxins (heteropodatoxin, hongatoxin, and blood depressing substance) that block K(v)4.x, K(v)1.1, -1.2, -1.3, and -3.4 in a highly selective manner as well as H(2)O(2) and tetraethylammonium, did not affect the current. Drugs with K(v)1.5-blocking properties (flecainide, perhexiline, and the novel atrial-selective antiarrhythmic 2'-{2-(4-methoxyphenyl)-acetylamino-methyl}-biphenyl-2-carboxylic acid (2-pyridin-3-yl-ethyl)-amide; AVE0118) inhibited I(K,PO) (IC(50) of 132 +/- 47, 17 +/- 10, and 1.25 +/- 0.62 microM, respectively). 4-Aminopyridine suppressed the current and accelerated its decay, reducing charge carriage with an IC(50) of 39 +/- 15 microM. Porcine-specific K(v) channel subunit sequences were cloned to permit real-time quantitative reverse transcription-polymerase chain reaction on RNA extracted from isolated cardiomyocytes, which showed much greater abundance of K(v)1.5 mRNA compared with K(v)1.4, K(v)4.2, and K(v)4.3. Action potential recordings showed that I(K,PO) inhibition with 0.1 mM 4-AP delayed repolarization (e.g., action potential duration at -50 mV increased from 45 +/- 9 to 69 +/- 5 ms at 3 Hz; P < 0.05). In conclusion, porcine atrium displays a current that is involved in repolarization, inactivates more slowly than classic transient outward current, is associated with strong K(v)1.5 expression, and shows a pharmacological profile typical of K(v)1.5-dependent currents.

Authors+Show Affiliations

Division of Cardiology, J.W. Goethe-University, Theodor Stern Kai 7, 60590 Frankfurt, Germany. j.ehrlich@em.uni-frankfurt.deNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

16916995

Citation

Ehrlich, Joachim R., et al. "Properties of a Time-dependent Potassium Current in Pig Atrium: Evidence for a Role of Kv1.5 in Repolarization." The Journal of Pharmacology and Experimental Therapeutics, vol. 319, no. 2, 2006, pp. 898-906.
Ehrlich JR, Hoche C, Coutu P, et al. Properties of a time-dependent potassium current in pig atrium: evidence for a role of kv1.5 in repolarization. J Pharmacol Exp Ther. 2006;319(2):898-906.
Ehrlich, J. R., Hoche, C., Coutu, P., Metz-Weidmann, C., Dittrich, W., Hohnloser, S. H., Nattel, S., & Gögelein, H. (2006). Properties of a time-dependent potassium current in pig atrium: evidence for a role of kv1.5 in repolarization. The Journal of Pharmacology and Experimental Therapeutics, 319(2), 898-906.
Ehrlich JR, et al. Properties of a Time-dependent Potassium Current in Pig Atrium: Evidence for a Role of Kv1.5 in Repolarization. J Pharmacol Exp Ther. 2006;319(2):898-906. PubMed PMID: 16916995.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Properties of a time-dependent potassium current in pig atrium: evidence for a role of kv1.5 in repolarization. AU - Ehrlich,Joachim R, AU - Hoche,Christin, AU - Coutu,Pierre, AU - Metz-Weidmann,Christiane, AU - Dittrich,Werner, AU - Hohnloser,Stefan H, AU - Nattel,Stanley, AU - Gögelein,Heinz, Y1 - 2006/08/17/ PY - 2006/8/19/pubmed PY - 2006/12/9/medline PY - 2006/8/19/entrez SP - 898 EP - 906 JF - The Journal of pharmacology and experimental therapeutics JO - J Pharmacol Exp Ther VL - 319 IS - 2 N2 - Cardiac electrical activity is modulated by potassium currents. Pigs have been used for antiarrhythmic drug testing, but only sparse data exist regarding porcine atrial ionic electrophysiology. Here, we used electrophysiological, molecular, and pharmacological tools to characterize a prominent porcine outward K(+) current (I(K,PO)) in atrial cardiomyocytes isolated from adult pigs. I(K,PO) activated rapidly (time to peak at +60 mV; 2.1 +/- 0.2 ms), inactivated slowly (tau(f) = 45 +/- 10; tau(s) = 215 +/- 28 ms), and showed very slow recovery (tau(f) = 1.54 +/- 0.73 s; tau(s) = 7.91 +/- 1.78 s; n = 9; 36 degrees C). Activation and inactivation were voltage-dependent, and current properties were consistent with predominant K(+) conductance. Neurotoxins (heteropodatoxin, hongatoxin, and blood depressing substance) that block K(v)4.x, K(v)1.1, -1.2, -1.3, and -3.4 in a highly selective manner as well as H(2)O(2) and tetraethylammonium, did not affect the current. Drugs with K(v)1.5-blocking properties (flecainide, perhexiline, and the novel atrial-selective antiarrhythmic 2'-{2-(4-methoxyphenyl)-acetylamino-methyl}-biphenyl-2-carboxylic acid (2-pyridin-3-yl-ethyl)-amide; AVE0118) inhibited I(K,PO) (IC(50) of 132 +/- 47, 17 +/- 10, and 1.25 +/- 0.62 microM, respectively). 4-Aminopyridine suppressed the current and accelerated its decay, reducing charge carriage with an IC(50) of 39 +/- 15 microM. Porcine-specific K(v) channel subunit sequences were cloned to permit real-time quantitative reverse transcription-polymerase chain reaction on RNA extracted from isolated cardiomyocytes, which showed much greater abundance of K(v)1.5 mRNA compared with K(v)1.4, K(v)4.2, and K(v)4.3. Action potential recordings showed that I(K,PO) inhibition with 0.1 mM 4-AP delayed repolarization (e.g., action potential duration at -50 mV increased from 45 +/- 9 to 69 +/- 5 ms at 3 Hz; P < 0.05). In conclusion, porcine atrium displays a current that is involved in repolarization, inactivates more slowly than classic transient outward current, is associated with strong K(v)1.5 expression, and shows a pharmacological profile typical of K(v)1.5-dependent currents. SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/16916995/Properties_of_a_time_dependent_potassium_current_in_pig_atrium:_evidence_for_a_role_of_kv1_5_in_repolarization_ L2 - https://jpet.aspetjournals.org/cgi/pmidlookup?view=long&amp;pmid=16916995 DB - PRIME DP - Unbound Medicine ER -