In these experiments, the extracellular solution contained Ca
2+ (2 mM). TTX (1 μM) was present to block voltage-gated Na
+ currents, and 4-AP (5 mM) was present to block I
A in all experiments. In different sets of experiments, the extracellular solution also contained a blocker of one known type of K
Ca, so that the effect of haloperidol on the other type of K
Ca could be tested specifically. For example, the experimental solution in
Figure 8A contained apamin (300 nM) in addition to TTX and 4-AP to block SK-type K
Ca channels.
16 Figure 8A shows outward currents evoked by a voltage command to +30 mV from a holding potential of −70 mV. Under the experimental conditions, the evoked current is expected to consist of the persistent component of the voltage-gated K
+ current and K
Ca flowing through BK-type channels. Haloperidol had little effect on the amplitude of the outward current. This small effect might be expected if the evoked outward current consisted entirely of the persistent component of the voltage-gated K
+ current. However, the subsequent application of CTX (100 nM, a blocker of BK-type K
Ca channels
16 ) in the continuous presence of 10 nM haloperidol reduced the outward currents by 25.1% (
Fig. 8A , 10 nM Haloperidol + Charybdotoxin). This result demonstrates that BK-type channels, in fact, contributed to the outward current in
Figure 8A , but that these channels were little affected by 10 nM haloperidol. The average reduction of the outward current by 10 nM haloperidol under the experimental conditions in
Figure 8A was 4.1% ± 1.6% (
n = 4), whereas 100 nM CTX (plus haloperidol) reduced the outward current by 20.1% ± 8.6% (
n = 4). The high affinity of CTX for its respective channels made it difficult to wash out.
17 18