A1 adenosine receptor-mediated GIRK channels contribute to the resting conductance of CA1 neurons in the dorsal hippocampus

Abstract

The dorsal and ventral hippocampi are functionally and anatomically distinct. Recently, we reported that dorsal Cornu Ammonis area 1 (CA1) neurons have a more hyperpolarized resting membrane potential and a lower input resistance and fire fewer action potentials for a given current injection than ventral CA1 neurons. Differences in the hyperpolarization-activated cyclic nucleotide-gated cation conductance between dorsal and ventral neurons have been reported, but these differences cannot fully account for the different resting properties of these neurons. Here, we show that coupling of A1 adenosine receptors (A1ARs) to G-protein-coupled inwardly rectifying potassium (GIRK) conductance contributes to the intrinsic membrane properties of dorsal CA1 neurons but not ventral CA1 neurons. The block of GIRKs with either barium or the more specific blocker Tertiapin-Q revealed that there is more resting GIRK conductance in dorsal CA1 neurons compared with ventral CA1 neurons. We found that the higher resting GIRK conductance in dorsal CA1 neurons was mediated by tonic A1AR activation. These results demonstrate that the different resting membrane properties between dorsal and ventral CA1 neurons are due, in part, to higher A1AR-mediated GIRK activity in dorsal CA1 neurons.

The Roles of Gβγ and Gα in Gating and Regulation of GIRK Channels

“…The extent of GPCR-and Gβγ-dependence of this activity is not clear in most cases. For instance, I basal recorded in cell-attached patches in dendrites of CA1 hippocampal neurons appeared to be GPCR-independent (Chen & Johnston, 2005), whereas whole-cell recordings in dorsal CA1 neurons suggested that most of I basal was elicited by ambient tonic A1 adenosine receptor activation (Kim & Johnston, 2015). Whatever the nature of I basal in the brain, it certainly carries important physiological functions.…”

Environmental enrichment modulates intrinsic cellular excitability of hippocampal CA1 pyramidal cells in a housing duration and anatomical location-dependent manner

“…First, the IR modulation could be due to a regulation of the leak conductance such as the G protein-coupled inwardly rectifying K + (GIRK) channels or two-pore domain K + (K2P) channels. Currents mediated by these channels contribute to IR and could be measured with whole-cell configuration [27,34]. Among these two, GIRK channels are more densely distributed in dorsal compared to ventral CA1 [27].…”

“…Currents mediated by these channels contribute to IR and could be measured with whole-cell configuration [27,34]. Among these two, GIRK channels are more densely distributed in dorsal compared to ventral CA1 [27]. Therefore, a modulation of GIRK channels could potentially cause a larger increase in excitability in dorsal CA1 cells.…”

GIRK Channels

“…For example, GIRK channels are expressed in the hippocampus Karschin et al, 1996;Koyrakh et al, 2005;Luscher et al, 1997), a region that is critical for spatial navigation and contextual learning as well as a key contributor to context-induced relapse in rodent models of drug seeking (Bossert & Stern, 2014;Gould & Leach, 2014;Isokawa, 2012;Luo, Tahsili-Fahadan, Wise, Lupica, & AstonJones, 2011). In addition to mediating the postsynaptic inhibitory effects of neurotransmitters (Luscher et al, 1997), GIRK channels in CA1 hippocampal neurons have a resting potassium conductance (Kim & Johnston, 2015). Interestingly, this resting GIRK conductance is higher for neurons in the dorsal hippocampus compared to those in the ventral hippocampus, and this difference is thought to contribute to the more hyperpolarized resting membrane potential observed in dorsal CA1 neurons (Kim & Johnston, 2015).…”

“…In addition to mediating the postsynaptic inhibitory effects of neurotransmitters (Luscher et al, 1997), GIRK channels in CA1 hippocampal neurons have a resting potassium conductance (Kim & Johnston, 2015). Interestingly, this resting GIRK conductance is higher for neurons in the dorsal hippocampus compared to those in the ventral hippocampus, and this difference is thought to contribute to the more hyperpolarized resting membrane potential observed in dorsal CA1 neurons (Kim & Johnston, 2015). This suggests that GIRK-mediated currents contribute to the different functional properties of these two subregions and potentially the distinct roles they are thought to play in hippocampal-dependent behaviors (Fanselow & Dong, 2010).…”