Radial arteries (RAs) and internal mammary arteries (IMAs) are commonly used in revascularisation surgery. Long term patency and survival of IMA grafts is good, but RAs are prone to vasospasm, which limits their use. The use of calcium channel blockers and nitrates to prevent RA spasm has been suggested to improve results (Chanda et al. 2000; Kalus et al. 2001) and a recent study suggests that K⁺ channel openers may also be effective (Hamilton et al. 2002). In order to better target and treat the vasospasm, a clearer understanding of the mechanisms that control tone in these vessels is needed.

In this study we compared the K⁺ channels expressed in smooth muscle cells (SMCs) from human RAs and IMAs, using the whole-cell patch-clamp technique, with the aim of identifying differences that could account for the RA-specific vasospasm. Vessels were obtained from consenting patients undergoing coronary artery bypass surgery. Results are reported as means ± S.E.M. Data were compared using Student’s paired t test and the level of significance set at P < 0.05.

SMCs isolated from RAs and IMAs had similar input resistances (IMA, 7 ± 3 GV, n = 30; RA, 10 ± 3 GV, n = 42), membrane capacitance (IMA, 31 ± 3 pA pF^-1, n = 30; RA, 28 ± 2 pA pF^-1, n = 42) and resting membrane potentials (IMA, -41 ± 5 mV, n = 12; RA, -48 ± 3 mV, n = 35). Macroscopic K⁺ currents were activated upon stepping to test potentials ²ge³ -30 mV and in cells from both vessels the currents displayed similar kinetics and peak amplitudes (at 40 mV IMA, 39 ± 9 pA pF^-1, n = 26; RA, 58 ± 9 pA pF^-1, n = 35). At concentrations up to 10 mM, 4-aminopyridine had no consistent effect on the current recorded from IMA cells (n = 7), but at 10 mM it caused significant inhibition of the current in RA cells (37 ± 10 % at 40 mV, P < 0.05, n = 7). The effect on RA cells was, however, variable, with no effect in one cell and inhibition ranging from 13 to 81 % in six others. The effects of a number of inhibitors of Ca²⁺-activated K⁺ channels were also tested: iberiotoxin (100 nM), charybdotoxin (100 nM), apamin (50 nM) and clotrimazole (1-10 µM). Each drug was tested on cells from at least three RAs and three IMAs. Only charybdotoxin caused consistent inhibition of the current in either vessel. Its effects were concentration dependent and of similar magnitude in each vessel type. At 40 mV, it reduced current amplitude by 64 % in IMA cells (from 22 ± 6 to 8 ± 1 pA pF^-1; n = 5, P < 0.05) and 67 % in RA cells (from 13 ± 2 to 4 ± 1 pA pF^-1; n = 6, P < 0.05). The currents were consistently noisy and single-channel recordings in excised membrane patches showed that the predominant K⁺ channel had a large conductance (198 ± 9 pS, n = 11; RAs) and was acutely sensitive to the intracellular [Ca²⁺]. These properties suggest that large-conductance BK_Ca channels were the main mediators of the K⁺ current. This is despite the finding that iberiotoxin failed to inhibit it.

Overall, the results show that an iberiotoxin-insensitive, large-conductance Ca²⁺-activated K⁺ channel mediates most of the K⁺ current in smooth muscle cells from human IMAs and RAs. The only difference observed between cells from RAs and IMAs was the variable expression in RAs of a 4-aminopyridine-sensitive, voltage-gated K⁺ current.

This work was supported by the British Heart Foundation.