Figure 2.
Effects of the Ca2+ Antagonist Nifedipine on Spontaneous APs and [Ca2+]i Transients in Control and LQT2 iPS-CM
(A) Upper panel, time course of APs (Em) during superfusion with nifedipine (gray bar) in a representative control iPS-CM microcluster, with numerals to indicate regions of interest (ROI). Center and lower panels: labeled ROI shown on an expanded scale.
(B) Upper and center panels, equivalent plots to (A), from a representative LQT2 iPS-CM cluster. Note the increase in beating rate during nifedipine exposure (gray bar). Lower panel, [Ca2+]i transients (red, labeled Fluo, in arbitrary units) from ROI indicated by numerals above.
(C) APD90 in (A) and (B) plotted against elapsed time, defined by assigning the point of nifedipine addition (gray bar) to time zero. (Control responses occurred at negative values of elapsed time.) Note that, in the LQT2 microcluster, nifedipine reduced APD90 by 84% (to 0.71 ± 0.01 s), which was still longer than mean pre-nifedipine APD90 in the control microcluster.
(D) Changes in [Ca2+]i transients (Fluo, in arbitrary units; red trace) when an unpatched LQT2 microcluster was exposed to 2 μM nifedipine (gray bar), followed by 50 μM tetrodotoxin (TTX) in the continued presence of nifedipine (white bar), which arrested beating. Downward trace steps represent the blocking of excitation light by the shutter.