title: Calcium exerts a larger regulatory effect on potassium+ channels in small mesenteric artery mycoytes from spontaneously hypertensive rats compared to Wistar-Kyoto rats.
abstract: Hypertension is associated with a remodeling of arterial smooth muscle K(+) channels with Ca(2+)-gated K(+) channel (BK(Ca)) activity being enhanced and voltage-gated K(+) channel (K(v)) activity depressed. Because both of these channel types are modulated by intracellular Ca(2+), we tested the hypothesis that Ca(2+) had a larger effect on both BK(Ca) and K(v) channels in arterial myocytes from hypertensive animals. Myocytes were enzymatically dispersed from small mesenteric arteries (SMA) of 12-week-old Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). Using whole cell patch clamp methods, BK(Ca) and K(v) current components were determined as iberiotoxin-sensitive and -insensitive currents, respectively. The effects of Ca(2+) on these K(+) current components were determined from measurements made with 0.2 and 2 mmol/L external Ca(2+). Increasing external Ca(2+) from 0.2 to 2 mmol/L Ca(2+) increased BK(Ca) currents recorded using myocytes from both WKY rats and SHR with a larger effect in SHR. Increasing external Ca(2+) decreased K(v) currents recorded using myocytes from both WKY and SHR also with a larger effect in SHR. In other experiments, currents through voltage-gated Ca(2+) channels (Ca(v)) measured at 0.2 mmol/L external Ca(2+) were 12 +/- 2% (n = 12) of those recorded at 2 mmol/L Ca(2+) with no differences in percent effect between WKY and SHR. In isolated SMA segments, isometric force development in response to 140 mmol/L KCl at 0.2 mmol/L external Ca(2+) was about 23 +/- 6% (n = 8) of that measured at 2 mmol/L external Ca(2+). These results suggest that an increase in Ca(2+) influx through Ca(v) or in intracellular Ca(2+) secondary to an increase in external Ca(2+) augments BK(Ca) currents and inhibits K(v) currents in SMA myocytes with a larger effect in SHR compared to WKY. This mechanism may contribute to the functional remodeling of K(+) currents of arterial myocytes in hypertensive animals.
authors.affiliation: Lankenau Institute for Medical Research, Jefferson Health System, Philadelphia, Pennsylvania, USA. coxr@mlhs.org
authors.forename: Robert H
authors.initials: RH
authors.lastname: Cox
authors.forename: Irina
authors.initials: I
authors.lastname: Lozinskaya
authors.forename: Nancy J
authors.initials: NJ
authors.lastname: Dietz
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism; D006973:Hypertension / Q000378:metabolism*; D051036:Large-Conductance Calcium-Activated Potassium Channels; D008564:Membrane Potentials / Q000502:physiology; D008638:Mesenteric Arteries / Q000166:cytology / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism; D024681:Potassium Channels, Calcium-Activated / Q000378:metabolism; D024642:Potassium Channels, Voltage-Gated / Q000378:metabolism*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013045:Species Specificity
chemical_list: D015220:Calcium Channels; D051036:Large-Conductance Calcium-Activated Potassium Channels; D024681:Potassium Channels, Calcium-Activated; D024642:Potassium Channels, Voltage-Gated; D011188:Potassium; D002118:Calcium