Mutations known to affect Reaper’s cell killing
ability also affect K+ channel blocking ability.
(A) Blocking effects of Reaper N terminus peptides
(wild-type, F5A, and Y6A) on ShBΔ6–46:T449V currents. Currents
recorded from an inside-out patch at +50 mV are shown. Peptides were
applied at 100 μM. (B) Concentration dependence of the
channel block by the Reaper wild-type, F5A, and Y6A N terminus peptides
(mean ± SD, n = 5). Macroscopic
ShBΔ6–46:T449V currents were measured in response to depolarization
to +50 mV for 200 ms to 1.5 s in duration. Normalized steady-state
current amplitudes are plotted as a function of the peptide
concentration. (C) Rate constants
(kON and kOFF) of
the block by the Reaper wild-type, F5A, and Y6A N terminus peptides.
Rate constants were estimated by fitting the macroscopic current time
course in the presence of the peptides at 100 μM as described in
Materials and Methods. Values of the rate constants are
compared by using boxplots. (D) Recovery from the Reaper F5A
peptide-induced block is faster. Time course of recovery from
peptide-induced block was estimated by using a standard double-pulse
protocol. Two depolarizing pulses to +50 mV, separated by various
intervals as indicated, were applied. Relative current amplitudes,
amplitude elicited by the second pulse divided by that from the first
pulse, are plotted. Representative ShBΔ6–46:T449V currents recorded
in the presence of the Reaper F5A peptide during the second pulses to
+50 mV are shown (left). Recovery time courses observed with wild-type
and F5A Reaper peptides (100 μM) are compared (right; mean ±
SD, n = 3). Smooth lines represent single
exponential fits to the data. Recovery time constants for wild-type and
F5A Reaper were 70 ms and 30 ms, respectively. (E) The A11N
mutation does not affect the Reaper N terminus peptide’s ability to
block the channel. Reaper wild-type and A11N peptides were applied at
100 μM. The time courses of the currents recorded in the presence of
the two peptides were similar at all concentrations examined (1 to 100
μM, data not shown).