Altered prevalence of gating modes in neurotransmitter inhibition of N-type calcium channels

G protein-mediated inhibition of voltage-activated calcium channels by neurotransmitters has important consequences for the control of synaptic strength. Single-channel recordings of N-type calcium channels in frog sympathetic neurons reveal at least three distinct patterns of gating, designated low-Po, medium-Po, and high-Po modes according to their probability of being open (Po) at -10 millivolts. The high-Po mode is responsible for the bulk of divalent cation entry in the absence of neurotransmitter. Norepinephrine greatly decreased the prevalence of high-Po gating and increased the proportion of time a channel exhibited low-Po behavior or no activity at all, which thereby reduced the overall current. Directly observed patterns of transition between the various modes suggest that activated G protein alters the balance between modal behaviors that freely interconvert even in the absence of modulatory signaling.