Figure 5.

Effects of the T-type Ca²⁺ channel blockers mibefradil and pimozide. (a) In this original trace, an arteriole was stimulated repeatedly (12 stimulations of 40 s duration) with 75 mM K⁺ (K). After four stimulations mibefradil (1 μM) was applied for a total period of ∼10 min. The inhibition induced by mibefradil was maximal after three to four stimulations, and this time-independent effect is referred to as use-dependent block. (b) Open columns depict % inhibition of the first stimulation (initial block) and hatched columns depict inhibition of the last stimulation (use-dependent block) in the presence of mibefradil at all concentrations tested (n=4−5). The untreated control experiments are shown here as 0.0 μM mibefradil (n=4). (c) Ca²⁺ responses to 75 mM K⁺ (K) in an arteriole exposed to 500 nMof the antipsychotic pimozide, clearly showing a use-dependent effect of the drug. A small reversible decrease of the baseline ratio is seen after the addition of pimozide. (d) Summary of responses obtained in arterioles exposed to pimozide (n=4) and in vehicle control experiments (n=4). ^*P<0.05, ^**P<0.01, and ^*** P<0.001; t-test vs untreated or vehicle control experiments.