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. Author manuscript; available in PMC: 2024 Jun 1.
Published in final edited form as: Biol Psychiatry. 2021 Oct 16;93(11):1041–1052. doi: 10.1016/j.biopsych.2021.10.004

Figure 3.

Figure 3.

Decreased small conductance Ca2+-activated K+ channel function contributes to excitatory H2 receptor signaling in CINs. (A) Representative traces of VSAG in CINs following −200 pA and −400 pA current injection in ACSF (black), HA (light green), and dimaprit (dark green). (B) Average VSAG in ACSF, HA, or dimaprit following hyperpolarizing current steps (scale bars = 50 mV/100 ms). (C) Quantification of the maximum VSAG (at current injection = −400 pA) in ACSF or following each pharmacological manipulation (VSAG ACSF: 28.36 ± 4.87 mV, n = 9; VSAG HA: 30.63 ± 7.34 mV, n = 6; VSAG dimaprit: 30.92 ± 5.41 mV, n = 8; one-way analysis of variance, ACSF vs. drug, F2,20 = 0.66, Sidak’s post hoc, p = .979). (D) Representative traces (left) of VSAG before and after ZD7288 at approximately t = 20 minutes (†) obtained from separate CIN in Iclamp following −400 pA current step. Note absence of hyperpolarization-activated, cyclic nucleotide-gated cation-mediated VSAG. Normalized time-course summary (right) of sAP firing frequency during dimaprit application in the presence of ZD7288. (E) Normalized time-course summary of sAP firing frequency during dimaprit application in the presence of db-cAMP. (F) Normalized time-course summary of sAP firing frequency during dimaprit application in the presence of H89. (G) Quantification of average sAP firing at t(gray) following dimaprit in each pharmacological manipulation relative to ACSF (re-depicted from Figure 1L) (dimaprit in ZD7288: 359.30% ± 113.3%, n = 3, p = .580; dimaprit in db-cAMP: 417.7% ± 8.98%, n = 4, p = .974; dimaprit in H89: 359.11% ± 69.03%, n = 5, p = .483). (H) Representative traces of IHolding (VM = −70 mV) at baseline (ACSF) and in HA (black) or dimaprit (green) (scale bars = 40 pA/5 min). (I) Average IHolding before and after HA or dimaprit (HA IHolding: 101.70% ± 1.85%, n = 8, p = .542; dimaprit IHolding: 106.61% ± 75.14%, n = 8, p = .248). (J) Representative traces of sAPs in CINs exhibiting a high basal firing rate in ACSF (black) and the resulting dimaprit-induced transition to burst firing (green) (scale bars = 50 pA/3 s). (K) Normalized time-course summary (left) and quantification (right) of sAP firing frequency during dimaprit application in the presence of apamin (dimaprit in apamin: 168.40% ± 32.09%, n = 6, p = .002) (ACSF re-depicted from Figure 1L). (L) Representative traces of the voltage step-induced current response (scale bar = 500 pA/200 ms) and ITail at baseline (ACSF) (black) and following dimaprit (green) or apamin (gray) (ITail scale bars = 200 pA/50 ms). (M) Quantification of maximum ITail before and after dimaprit (peak ITail before dimaprit: 244.38 ± 28.07 pA; peak ITail after dimaprit: 209.6 ± 29.66 pA, n = 9, p = .017). Error bars indicate SEM. *p < .05. ACSF, artificial cerebrospinal fluid; AP, action potential; CIN, cholinergic interneuron; db-cAMP, dibutyryl cyclic adenosine monophosphate; Dim., dimaprit; HA, histamine; Max, maximum; sAP, spontaneous AP.