CA2-ACTIVATED K+ CHANNELS IN HUMAN SMOOTH-MUSCLE CELLS OF CORONARY ATHEROSCLEROTIC PLAQUES AND CORONARY MEDIA SEGMENTS()

The behavior of Ca2+-activated K+ channels of large conductance (BKCa) in smooth muscle cells, which were obtained from atherosclerotic plaq ue material (SMCP) and from media segments (SMCM) of human coronary ar teries, were compared using the patch-clamp technique. Voltage-clamp p rotocols in cell-attached patches revealed the characteristic voltage- dependent activation of BKCa in both cell groups. Single-channel condu ction was 216.4 +/- 16.7 pS (n = 6) in SMCP and 199.9 +/- 6.7 pS (n = 6) in SMCM in symmetrical 140 mM K+ solutions. Using outside-out patch es, external perfusion with 500 mu M tetraethylammonium ions caused a typical ''flickery block'' of the unitary current. The selective BKCa channel inhibitor iberiotoxin (50 nM) effectively blocked BKCa channel activity. Comparing BKCa open-state probabilities (P-0) at + 80 mV in cell-attached patches, a highly significant difference between SMCP ( P-0 = 0.1438 +/- 0.1301; n = 15) and SMCM (P-0 = 0.0093 +/- 0.0044; n = 15; Kruskal-Wallis test, p < 0.001) was found. In contrast to this f inding, there was no significant difference in the open-state probabil ity of BKCa between SMCP (P-0 = 0.0542 +/- 0.0237; n = 9) and SMCM (P- 0 = 0.0472 +/- 0.0218; n = 10; p = n.s.) using inside-out patches. The results show an interesting difference in the behavior of large condu ctance Ca2+-activated K+ channel in SMCP compared to SMCM with a signi ficantly higher channel activity in human smooth muscle cells obtained from coronary atherosclerotic plaque material. This finding may indic ate an important functional role of BKCa channels in the development o f atherosclerosis.