Muscarinic inhibition of M‐current and a potassium leak conductance in neurones of the rat basolateral amygdala.

1. Voltage‐clamp recordings using a single microelectrode were obtained from pyramidal neurones of the basolateral amygdala (BLA) in slices of the rat ventral forebrain. Slow inward current relaxations during hyperpolarizing voltage steps from a holding potential of ‐40 mV were identified as the muscarinic‐sensitive M‐current (IM), a time‐ and voltage‐dependent potassium current previously identified in other neuronal cell types. 2. Activation of IM was voltage dependent with a threshold of approximately ‐70 mV. At membrane potentials positive to this, the steady‐state current‐voltage (I‐V) relationship showed substantial outward rectification, reflecting the time‐ and voltage‐dependent opening of M‐channels. The underlying conductance (gM) also increased sharply with depolarization. 3. The reversal potential for IM was ‐84 mV in medium containing 3.5 mM K+. This was shifted positively by 27 mV when the external K+ concentration was raised to 15 mM. 4. The time courses of M‐current activation and deactivation were fitted by a single exponential. The time constant for IM decay, measured at 24 degrees C, was strongly dependent on membrane potential, ranging from 330 ms at ‐40 mV to 12 ms at ‐100 mV. 5. Bath application of carbachol (0.5‐40 microM) inhibited IM, as evidenced by the reduction or elimination of the slow inward M‐current relaxations evoked during hyperpolarizing steps from a holding potential of ‐40 mV. The outward rectification of the steady‐state I‐V relationship at membrane potentials positive to ‐70 mV was also largely eliminated. The inhibition of IM by carbachol was dose dependent and antagonized by atropine. 6. Carbachol produced an inward current shift at a holding potential of ‐40 mV that was only partially attributable to inhibition of IM. An inward current shift was also produced by carbachol at membrane potentials negative to ‐70 mV, where IM is inactive. These effects were dose dependent and antagonized by atropine. They were attributed to the muscarinic inhibition of a voltage‐insensitive potassium leak conductance (ILeak). 7. In most cells, carbachol reduced the slope of the instantaneous I‐V relationship obtained from a holding potential of ‐70 mV so that it crossed the control I‐V plot at the reversal potential for ILeak. This was found to be ‐108 mV in 3.5 mM K+ saline, shifting to ‐66 mV in 15 mM K+ saline.(ABSTRACT TRUNCATED AT 400 WORDS)