Figure 7.

Organic blockers of the K_ir channels. (A) with a GIRK current activated by a cholinergic muscarinic agonist (oxotremorine 10 μM), the GIRK channels blocker tertiapin-Q (1 μM) completely suppresses the current (n = 11; see text for explanation); tertiapin-Q alone does not change the amplitude of hyperpolarization-activated (not shown; n = 13). In this as in the following panels, the steady-state (ss) current is calculated in relation to membrane capacity. (B) Quinacrine (100 μM) inhibition of hyperpolarization-activated current (n = 15). (C) With the KIR2.x channels blocked by quinacrine, a muscarinic cholinergic agonist (oxotremorine 10 μM) can activate a GIRK current (yellow dots), and this fraction can be completely suppressed by tertiapin (green dots; n = 7). ^*, ^** and ^*** indicate significance levels of 0.05, 0.01 and 0.001, respectively. (D) Effect of quinacrine on membrane potential. Perforated patch recording in standard saline (EC1 solution). The blue bar indicates the time of application of 100 μM into the bath; to the right, a sequence recorded after injection of 35 pA hyperpolarizing current; (further explanation in the text). All recordings were realized at 34°C, in EC2, BL1, and BL2; statistical analysis performed with Two-Way ANOVA and post-hoc Bonferroni test.