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 Ca2+-gated K+ channel (BKCa) activity being enhanced and voltage-gated K+ channel (Kv) activity depressed. Because both of these channel types are modulated by intracellular Ca2+, we tested the hypothesis that Ca2+ had a larger effect on both BKCa and Kv channels in arterial myocytes from hypertensive animals. Myoctyes 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, BKCa and Kv current components were determined as iberiotoxin-sensitive and -insensitive currents, respectively. The effects of Ca2+ on these K+ current components were determined from measurements made with 0.2 and 2 mmol/L external Ca2+. Increasing external Ca2+ from 0.2 to 2 mmol/L Ca2+ increased BKCa currents recorded using myocytes from both WKY rats and SHR with a larger effect in SHR. Increasing external Ca2+ decreased Kv currents recorded using myocytes from both WKY and SHR also with a larger effect in SHR. In other experiments, currents through voltage-gated Ca2+ channels (Cav) measured at 0.2 mmol/L external Ca2+ were 12 ± 2% (n = 12) of those recorded at 2 mmol/L Ca2+ 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 Ca2+ was about 23 ± 6% (n = 8) of that measured at 2 mmol/L external Ca2+. These results suggest that an increase in Ca2+ influx through Cav or in intracellular Ca2+ secondary to an increase in external Ca2+ augments BKCa currents and inhibits Kv 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.