Structure and function of cardiac potassium channels
- PMID: 10533574
- DOI: 10.1016/s0008-6363(99)00071-1
Structure and function of cardiac potassium channels
Abstract
Recent advances in molecular biology have had a major impact on our understanding of the biophysical and molecular properties of ion channels. This review is focused on cardiac potassium channels which, in general, serve to control and limit cardiac excitability. Approximately 60 K+ channel subunits have been cloned to date. The (evolutionary) oldest potassium channel subunits consist of two transmembrane (Tm) segments with an intervening pore-loop (P). Channels formed by four 2Tm-1P subunits generally function as inwardly rectifying K(+)-selective channels (KirX.Y): they conduct substantial current near the resting potential but carry little or no current at depolarized potentials. The inward rectifier IK1 and the ligand-gated KATP and KACh channels are composed of such subunits. The second major class of K+ channel subunits consists of six transmembrane segments (S1-S6). The S5-P-S6 section resembles the 2Tm-1P subunit, and the additional membrane-spanning segments (especially the charged S4 segment) endow these 6Tm-1P channels with voltage-dependent gating. For both major families, four subunits assemble into a homo- or heterotetrameric channel, subject to specific subunit-subunit interactions. The 6Tm-1P channels are closed at the resting potential, but activate at different rates upon depolarization to carry sustained or transient outward currents (the latter due to inactivation by different mechanisms). Cardiac cells typically display at least one transient outward current and several delayed rectifiers to control the duration of the action potential. The molecular basis for each of these currents is formed by subunits that belong to different Kvx.y subfamilies and alternative splicing can contribute further to the diversity in native cells. These subunits display distinct pharmacological properties and drug-binding sites have been identified. Additional subunits have evolved by concatenation of two 2Tm-1P subunits (4Tm-2P); dimers of such subunits yield voltage-independent leak channels. A special class of 6Tm-1P subunits encodes the 'funny' pacemaker current which activates upon hyperpolarization and carries both Na+ and K+ ions. The regional heterogeneity of K+ currents and action potential duration is explained by the heterogeneity of subunit expression, and significant changes in expression occur in cardiac disease, most frequently a reduction. This electrical remodelling may also be important for novel antiarrhythmic therapeutic strategies. The recent crystallization of a 2Tm-1P channel enhances the outlook for more refined molecular approaches.
Similar articles
-
Pharmacology of cardiac potassium channels.Adv Pharmacol. 2010;59:93-134. doi: 10.1016/S1054-3589(10)59004-5. Adv Pharmacol. 2010. PMID: 20933200 Review.
-
Structure and function of potassium channels in plants: some inferences about the molecular origin of inward rectification in KAT1 channels (Review).Mol Membr Biol. 2003 Jan-Mar;20(1):19-25. doi: 10.1080/0968768021000057371. Mol Membr Biol. 2003. PMID: 12745922 Review.
-
Myocardial potassium channels: electrophysiological and molecular diversity.Annu Rev Physiol. 1996;58:363-94. doi: 10.1146/annurev.ph.58.030196.002051. Annu Rev Physiol. 1996. PMID: 8815800 Review.
-
Pharmacological Conversion of a Cardiac Inward Rectifier into an Outward Rectifier Potassium Channel.Mol Pharmacol. 2016 Sep;90(3):334-40. doi: 10.1124/mol.116.104950. Epub 2016 May 31. Mol Pharmacol. 2016. PMID: 27247338 Review.
-
Pharmacology of cardiac potassium channels.Cardiovasc Res. 2004 Apr 1;62(1):9-33. doi: 10.1016/j.cardiores.2003.12.026. Cardiovasc Res. 2004. PMID: 15023549 Review.
Cited by
-
Guanidine affects differentially the twitch response of diaphragm, extensor digitorum longus and soleus nerve-muscle preparations of mice.Molecules. 2012 Jun 15;17(6):7503-22. doi: 10.3390/molecules17067503. Molecules. 2012. PMID: 22706376 Free PMC article.
-
Does lindane (gamma-hexachlorocyclohexane) increase the rapid delayed rectifier outward K+ current (IKr) in frog atrial myocytes?BMC Pharmacol. 2002 Jul 10;2:15. doi: 10.1186/1471-2210-2-15. BMC Pharmacol. 2002. PMID: 12106504 Free PMC article.
-
Voltage-Gated Sodium Channel β1/β1B Subunits Regulate Cardiac Physiology and Pathophysiology.Front Physiol. 2018 Apr 23;9:351. doi: 10.3389/fphys.2018.00351. eCollection 2018. Front Physiol. 2018. PMID: 29740331 Free PMC article. Review.
-
The molecular basis of cardiac arrhythmias in patients with cardiomyopathy.Curr Heart Fail Rep. 2004 Sep;1(3):98-103. doi: 10.1007/s11897-004-0018-3. Curr Heart Fail Rep. 2004. PMID: 16036032 Review.
-
Sex hormones and the QT interval: a review.J Womens Health (Larchmt). 2012 Sep;21(9):933-41. doi: 10.1089/jwh.2011.3444. Epub 2012 Jun 4. J Womens Health (Larchmt). 2012. PMID: 22663191 Free PMC article. Review.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources