Figure 7. Tachycardia-dependent upregulation of small-conductance Ca2+-activated K+ (SK)-channels.

A, Voltage- or current-clamp protocols (V-Clamp and C-clamp, respectively) comparing baseline conditions with conditions after 10-minutes of depolarizing V-Clamp pulses mimicking action potentials (APs) delivered at 5-Hz. B, Apamin (100-nmol/L)-sensitive I_SK at +80 mV in right-atrial (RA)-cardiomyocytes from Ctl-patients at baseline (open symbols) and from RA-cardiomyocytes from Ctl- or cAF-patients after 10-minutes of 5-Hz activation (diagonal-patterned bars). C, Representative APs in RA-cardiomyocytes from Ctl-patients at baseline or after 10-minutes stimulation at 5-Hz in the absence or presence of apamin (left), as well as apamin-induced prolongation of APD at 50% or 90% of repolarization (APD₅₀ and APD₉₀, respectively). D, Apamin-sensitive I_SK at +80 mV in RA-cardiomyocytes from Ctl-patients after 10-minutes of 5-Hz activation after pre-incubation with the Ca²⁺-chelator BAPTA (30-μmol/L for 1-hour), L-type Ca²⁺-channel blocker nifedipine (1-μmol/L for 3 mins), PP2A-inhibitor okadaic acid (10-nmol/L for 1-hour) or casein kinase type-II inhibitor TBBz (10-μmol/L for 1-hour) (green bars; all affecting SK-channel gating), or latrunculin-A (1-μmol/L for 2-hours) and primaquine (120-μmol/L for 4-hours) (orange bars; both affecting SK-channel trafficking). N-numbers indicate numbers of cardiomyocytes/patients. P-values are based on multilevel mixed models with log-transformed data to account for non-independent measurements in multiple cells from individual patients and are Bonferroni-corrected to account for multiple comparisons.