Dopamine modulates inwardly rectifying hyperpolarization-activated current (Ih) in cultured rat olfactory receptor neurons

The presence of dopamine receptors in olfactory receptor neurons (ORNs) suggests that odor sensitivity may be modulated by neurotransmitters at the level of primary sensory neurons. Using standard patch-clamp techniques on rat ORNs, we found that 1 mu M dopamine, 500 mu M SQ 22536 (SQ, an adenylyl cyclase inhibitor), 20 and 50 mu M quinpirole (a selective dopamine D-2 receptor agonist), and 1 mM adenosine 3',5'-cyclic monophosphate (cAMP) modulate the hyperpolarization-activated current I-h. On hyperpolarizing from a holding potential of -58 mV, a small Cs+-sensitive inwardly rectifying current (I-h) was observed. Increases in extracellular K+ increased I-h amplitude without shifting its voltage dependence of activation, whereas increases in temperature produced an increase in I-h amplitude and a hyperpolarizing shift in the activation curve. Application of 1 mu M dopamine reversibly shifted I-h activation to more negative potentials and decreased I-h current amplitudes. These effects were blocked by concomitant application of dopamine with sulpiride, a selective dopamine D-2 receptor antagonist. The effects of dopamine were mimicked by quinpirole. Quinpirole (20 mu M) decreased I-h current amplitude, but was without effect on a voltage dependence of activation. However, 50 mu M quinpirole produced both a reduction of I-h peak currents and a hyperpolarizing shift in the activation curve for I-h External application of the adenylyl cyclase inhibitor SV 22536 produced a reversible decrease in peak currents but had no effect on I-h voltage dependence of activation, whereas internal application of cAMP shifted I-h activation to more depolarized potentials. Because I-h modulates cell excitability and spike frequency adaptation, our findings support a role for dopamine in modulating the sensitivity and output of rat ORNs to odorants.