Russo MJ, Yau H-J, Nunzi M-G, Mugnaini E, Martina M. Dynamic metabotropic control of intrinsic firing in cerebellar unipolar brush cells. J Neurophysiol 100: 3351-3360, 2008. First published October 22, 2008 doi:10.1152/jn.90533.2008. Neuronal firing is regulated by the complex interaction of multiple depolarizing and hyperpolarizing currents; intrinsic firing, which defines the neuronal ability to generate action potentials in the absence of synaptic excitation, is particularly sensitive to modulation by currents that are active below the action potential threshold. Cerebellar unipolar brush cells (UBCs) are excitatory granule layer interneurons that are capable of intrinsic firing; here we show that, in acute mouse cerebellar slices, barium-sensitive background potassium channels of UBCs effectively regulate intrinsic firing. We also demonstrate that these channels are regulated by group II metabotropic glutamate receptors (mGluRs), which we show to be present in both of the known subsets of UBCs, one of which expresses calretinin and the other mGluR1␣. Finally, we show that background potassium currents controlling UBCs' firing are mediated by at least two channel types, one of which is sensitive and the other insensitive to the GIRK blocker tertiapin. Thus in UBCs, glutamatergic transmission appears to have a complex bimodal effect: although it increases spontaneous firing through activation of ionotropic receptors, it also has inhibitory effects through the mGluRdependent activation of tertiapin-sensitive and -insensitive background potassium currents.
I N T R O D U C T I O NOne of the most intriguing electrophysiological properties of neural cells is the ability of some types of neuron to fire action potentials in the absence of excitatory synaptic inputs. Whereas the generation of action potentials is exclusively mediated by voltage-gated channels (Hille 2001), the values of resting membrane potential and input resistance, both of which are important in determining the ability of a neuron to fire spontaneously, are determined by the complex interplay of multiple voltage-gated and voltage-independent (leak) conductances (Jackson et al. 2004;Meuth et al. 2006;Raman et al. 2000;Russo et al. 2007). In most neurons the value of the resting membrane potential is more negative than the action potential threshold, due to the dominant role played by potassiumselective channels among the leakage conductances (Hodgkin and Huxley 1952;Millar et al. 2000;Talley et al. 2000;Taverna et al. 2005). Most of the potassium-selective channels that are open at rest are members of either one of two major families, KCNK and KCNJ. KCNK channels are voltageindependent channels that are modulated by an unusually large array of chemical, thermal, and mechanical stimuli (Lesage 2003). The KCNJ family comprises the inward rectifiers, some of which are regulated by metabotropic ␥-aminobutyric acid (GABA) and glutamate receptors through G proteins (Hille 1992;Saugstad et al. 1996).Cerebellar unipolar brush cells (UBCs) are excitatory i...