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Differences in K+ current components in mesenteric artery myocytes from WKY and SHR.
Am J Hypertens. 2001 Sep; 14(9 Pt 1):897-907.AJ

Abstract

Previous studies have documented increased K+ permeability of arterial smooth muscle in hypertension and suggested a role in altered arterial contractile function. To characterize the mechanisms responsible for these alterations, we determined the contribution of K+ current (IK) components to whole cell IK in freshly dispersed myocytes and tetraethylammonium (TEA)-induced contractile responses in mesenteric arteries of Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). Tetraethylammonium produced a larger tonic contractile response in SHR with a lower threshold compared to WKY (ie, 0.1 v 1 mmol/L), which was due in part to the larger Ca2+ current in SHR. Whole cell IK recorded by perforated patch methods was similar at a holding potential (HP) of -60 mV (IK60), but were larger in SHR when recorded from a HP of -20 mV (IK20). The selective blocker iberiotoxin (IbTX) was used to separate the contribution of voltage- (Kv) and calcium-dependent (KCa) components of IK60. The IK60 and IK20 component inhibited by 100 nmol/L IbTX (ie, KCa) was larger in SHR than in WKY myocytes, whereas the IbTX-insensitive IK60 component (ie, Kv) was larger in WKY. In the presence of IbTX, 1 and 10 mmol/L TEA inhibited a larger fraction of IK60 in SHR myocytes compared with WKY. The activation properties of the TEA-sensitive and TEA-insensitive Kv components determined by fitting a Boltzmann activation function to the current-voltage data, exhibited both group and treatment differences in the half maximal activation voltage (V0.5). The V0.5 of the TEA-sensitive Kv component was more positive than that of the TEA-insensitive component in both groups, and values for the V0.5 of both TEA-sensitive and TEA-insensitive components were more negative in SHR than WKY. These results show that SHR myocytes have larger KCa and smaller Kv current components compared with WKY. Furthermore, SHR myocytes have a larger TEA-sensitive Kv component. These differences may contribute to the differences in TEA contractions, resting membrane potential, Ca2+ influx, and KCa current reported in hypertensive arteries.

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Publisher Full Text

Authors+Show Affiliations

Cox RH
Department of Physiology, University of Pennsylvania, Philadelphia, USA.
Lozinskaya I
No affiliation info available
Dietz NJ
No affiliation info available

MeSH

AnimalsCalcium ChannelsDisease Models, AnimalDose-Response Relationship, DrugHypertensionMaleMesenteric ArteriesMuscle, Smooth, VascularMyocardial ContractionPotassium Channel BlockersPotassium ChannelsRatsRats, Inbred SHRRats, Inbred WKYSensitivity and SpecificityTetraethylammonium

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

11587156

Citation

Cox, R H., et al. "Differences in K+ Current Components in Mesenteric Artery Myocytes From WKY and SHR." American Journal of Hypertension, vol. 14, no. 9 Pt 1, 2001, pp. 897-907.
Cox RH, Lozinskaya I, Dietz NJ. Differences in K+ current components in mesenteric artery myocytes from WKY and SHR. Am J Hypertens. 2001;14(9 Pt 1):897-907.
Cox, R. H., Lozinskaya, I., & Dietz, N. J. (2001). Differences in K+ current components in mesenteric artery myocytes from WKY and SHR. American Journal of Hypertension, 14(9 Pt 1), 897-907.
Cox RH, Lozinskaya I, Dietz NJ. Differences in K+ Current Components in Mesenteric Artery Myocytes From WKY and SHR. Am J Hypertens. 2001;14(9 Pt 1):897-907. PubMed PMID: 11587156.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Differences in K+ current components in mesenteric artery myocytes from WKY and SHR. AU - Cox,R H, AU - Lozinskaya,I, AU - Dietz,N J, PY - 2001/10/6/pubmed PY - 2002/3/7/medline PY - 2001/10/6/entrez SP - 897 EP - 907 JF - American journal of hypertension JO - Am J Hypertens VL - 14 IS - 9 Pt 1 N2 - Previous studies have documented increased K+ permeability of arterial smooth muscle in hypertension and suggested a role in altered arterial contractile function. To characterize the mechanisms responsible for these alterations, we determined the contribution of K+ current (IK) components to whole cell IK in freshly dispersed myocytes and tetraethylammonium (TEA)-induced contractile responses in mesenteric arteries of Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). Tetraethylammonium produced a larger tonic contractile response in SHR with a lower threshold compared to WKY (ie, 0.1 v 1 mmol/L), which was due in part to the larger Ca2+ current in SHR. Whole cell IK recorded by perforated patch methods was similar at a holding potential (HP) of -60 mV (IK60), but were larger in SHR when recorded from a HP of -20 mV (IK20). The selective blocker iberiotoxin (IbTX) was used to separate the contribution of voltage- (Kv) and calcium-dependent (KCa) components of IK60. The IK60 and IK20 component inhibited by 100 nmol/L IbTX (ie, KCa) was larger in SHR than in WKY myocytes, whereas the IbTX-insensitive IK60 component (ie, Kv) was larger in WKY. In the presence of IbTX, 1 and 10 mmol/L TEA inhibited a larger fraction of IK60 in SHR myocytes compared with WKY. The activation properties of the TEA-sensitive and TEA-insensitive Kv components determined by fitting a Boltzmann activation function to the current-voltage data, exhibited both group and treatment differences in the half maximal activation voltage (V0.5). The V0.5 of the TEA-sensitive Kv component was more positive than that of the TEA-insensitive component in both groups, and values for the V0.5 of both TEA-sensitive and TEA-insensitive components were more negative in SHR than WKY. These results show that SHR myocytes have larger KCa and smaller Kv current components compared with WKY. Furthermore, SHR myocytes have a larger TEA-sensitive Kv component. These differences may contribute to the differences in TEA contractions, resting membrane potential, Ca2+ influx, and KCa current reported in hypertensive arteries. SN - 0895-7061 UR - https://www.unboundmedicine.com/medline/citation/11587156/Differences_in_K+_current_components_in_mesenteric_artery_myocytes_from_WKY_and_SHR_ L2 - https://academic.oup.com/ajh/article-lookup/doi/10.1016/s0895-7061(01)02145-8 DB - PRIME DP - Unbound Medicine ER -