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Introduction Peripheral somatosensory neurons sense and transmit all types of tactile, temperature, and chemical information from the environment and viscera to the CNS. A subset of these neurons (known as “nociceptive” neurons) specifically respond to tissue damage and can mediate sensation of pain. Therefore, understanding the mechanisms controlling the excitability of somatosensory neurons holds the key to the understanding of somatic sensation and pain. Extensive research worldwide uses electrophysiological recordings from these sensory neurons in order to study their excitability; however, a large share of such recordings is routinely carried out using dissociated and cultured sensory neuron preparations. This is in contrast to the research in the CNS where the “gold standard” is a recording from the acute slices of a particular brain or spinal cord region. Several anatomical features of the sensory ganglia make slice recording particularly difficult including the small size of the ganglia and “wrapping” of individual neuronal cell bodies by a satellite glia cell sheath. However, cultured neurons are subject to various shortand long-term changes (such as axotomy, enzymatic treatment,

Nikita Gamper (ed.), Ion Channels: Methods and Protocols, Methods in Molecular Biology, vol. 998, DOI 10.1007/978-1-62703-351-0_25, © Springer Science+Business Media, LLC 2013

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mechanical stress, artificial environment) which can trigger differentiation of neurons from their native state and thus compromise the results of the investigation. In this chapter we describe the DRG slice preparation for electrophysiological recordings with an aim to allow recordings from an acute, enzyme-free preparation. Here we have adopted the technique developed in previous studies (1) to record M-type K+ current from the acutely sliced DRG preparation using the perforated patch-clamp approach. M current is a slow voltage-gated K+ current with a negative activation threshold (negative to-60 mV) which is increasingly recognized as one of the major regulators of nociceptive neuron resting membrane potential and excitability (2–9). M current is conducted by the members of Kv7 family of K+ channel proteins with five known subunits (Kv7.1–7.5). The Kv7.2 M channel subunit has recently been shown to be present at cell bodies of nociceptive DRG neurons (8, 9), nodes of Ranvier of myelinated sensory fibers (10, 11), as well as in unnmyelinated fibers and free nociceptive nerve endings in the skin (7); there is also evidence for the expression of other M channel subunits (Kv7.3 and Kv7.5) throughout the peripheral nociceptive pathways (8–10). Additionally, there is accumulating evidence for the presence of functional M channels in nociceptive fibers and nerve endings (5, 7, 12). However most patch-clamp recordings of M channels in sensory neurons were performed using DRG cell cultures (2–4, 8). Therefore, in order to investigate the presence of functional M channels in acute sensory neurons in their native environment,