Differences in K+ current components in mesenteric artery myocytes from WKY and SHR.
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.
Cox
R H
RH
Department of Physiology, University of Pennsylvania, Philadelphia, USA.
Lozinskaya
I
I
Dietz
N J
NJ
D000818:Animals; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006973:Hypertension / Q000378:metabolism; D008297:Male; D008638:Mesenteric Arteries / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009200:Myocardial Contraction / Q000187:drug effects; D026902:Potassium Channel Blockers / Q000008:administration & dosage; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012680:Sensitivity and Specificity; D019789:Tetraethylammonium / Q000008:administration & dosage
D015220:Calcium Channels; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D019789:Tetraethylammonium