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. 2011 May 3;9(5):e1001057. doi: 10.1371/journal.pbio.1001057

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Jackman et al.

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.

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(A) Changing the voltage of an HC (V_HC) shifts the activation of the voltage-gated Ca²⁺ current (I_Ca) in a cone, indicative of negative feedback. Data for (A) and (B) were from simultaneous patch clamp recordings from a synaptically connected HC and a cone in a slice from salamander retina. Top: Current-voltage (I-V) curves at three different values of V_HC. Bottom: I_Ca activation curves derived from these I-V curves (see Methods). I-V curves were generated by ramp depolarizations from −90 to 0 mV (0.5 mV/ms). I_Ca activation curves were obtained by subtracting the linear leak current from the total membrane current during the ramp. The resulting leak-subtracted I_Ca was normalized to the maximal I_Ca and plotted only over the voltage range where channels are activating (e.g., from −70 to −20 mV). Data are reported as mean ± SEM. (B) Same as (A), except with HEPES (10 mM) added to bath solution to block negative feedback. (C) AMPA (20 µM) elicits a voltage-independent conductance that increases with hyperpolarization. HEPES (10 mM) was added to the bath solution to block negative feedback. Traces represent average currents from five cones. Data for panels (C–H) were from patch clamp recordings from cones in flat-mounted salamander retinas. (D) NBQX (10 µM) reduces the voltage-independent conductance. HEPES was again added to the bath solution to block negative feedback. Traces represent average currents from 13 cones. (E, F) I-V curve of the voltage-independent conductance modulated by AMPA or NBQX. Difference currents were calculated from data in panels (C) and (D). Dashed lines are extrapolated linear fits to show reversal potentials. (G, H) Quantification of the average effect of AMPA (n = 5) or NBQX (n = 13) on the voltage-independent conductance. (I) L-type Ca²⁺ channels are not required for positive feedback. Left: The FM1-43 release rate in darkness is accelerated by adding high K⁺ (n = 9) or 20 µM AMPA (n = 16). Addition of nicardipine (100 µM) suppressed release in darkness (n = 7) and in high K⁺ (n = 3) but not in AMPA (n = 4).