Potassium channels Kv1.1, Kv1.2 and Kv1.6 influence excitability of rat visceral sensory neurons

Abstract

Voltage-gated potassium channels, Kv1.1, Kv1.2 and Kv1.6, were identified as PCR products from mRNA prepared from nodose ganglia. Immunocytochemical studies demonstrated expression of the proteins in all neurons from ganglia of neonatal animals (postnatal days 0-3) and in 85-90 % of the neurons from older animals (postnatal days 21-60). In voltage clamp studies, a-dendrotoxin (a-DTX), a toxin with high specificity for these members of the Kv1 family, was used to examine their contribution to K + currents of the sensory neurons. a-DTX blocked current in both A-and C-type neurons. The current had characteristics of a delayed rectifier with activation positive to _50 mV and little inactivation during 250 ms pulses. In current-clamp experiments a-DTX, used to eliminate the current, had no effect on resting membrane potential and only small effects on the amplitude and duration of the action potential of A-and C-type neurons. However, there were prominent effects on excitability. a-DTX lowered the threshold for initiation of discharge in response to depolarizing current steps, reduced spike after-hyperpolarization and increased the frequency/pattern of discharge of A-and C-type neurons at membrane potentials above threshold. Model simulations were consistent with these experimental results and demonstrated how the other major K + currents function in response to the loss of the a-DTX-sensitive current to effect these changes in action potential wave shape and discharge.

Kv1.1 Deletion Augments the Afferent Hypoxic Chemosensory Pathway and Respiration

“…Previous studies in rats showed that there was only a small effect on the duration or amplitude of the action potential when ␣-DTXsensitive channels were blocked (Glazebrook et al, 2002). This reflected the short duration of the action potential relative to the activation time of Kv1.1.…”

“…Kv1.1 activates sufficiently rapidly that its block reduces the depolarizing current necessary to elicit an action potential near threshold. Block of Kv1.1 also reduces the afterhyperpolarization, thus contributing to repetitive discharge (Glazebrook et al, 2002). These effects on visceral sensory neurons predicted that alterations in the autonomic nervous system may occur in Kv1.1-null mice and, possibly, in EA-1 individuals.…”

“…Block of Kv1.1 (toxin K-sensitive current) eliminates ϳ60 -70% of the ␣-DTX-sensitive current in visceral sensory neurons, with the remainder of ␣-DTX current presumably carried by the Kv1.2 and Kv1.6 channels that are also present in these neurons (Glazebrook et al, 2002). To verify that Kv1.1 was not replaced by upregulation of Kv1.2 and Kv1.6 expression, we evaluated the amplitude of the ␣-DTX-sensitive current in primary cultures from wild-type and null mice.…”

“…The functional basis for the EA-1 phenotype has been investigated using the Kv1.1-null mouse (Smart et al, 1998;Zhou et al, 1998) and, more recently, a mouse carrying the V408A EA-1 mutation (Herson et al, 2003). We previously demonstrated the presence of Kv1.1 in visceral sensory neurons (Andrews and Kunze, 2001;Glazebrook et al, 2002) associated with cardiorespiratory reflexes that are essential to cardiovascular and respiratory homeostasis. Using both experimental and modeling approaches, we showed elimination of Kv1.1 increased excitability of these neurons.…”

Morphological and functional diversity of first-order somatosensory neurons

“…Many sensory neurons are sensitive to the dendrotoxins that inhibit K V 1 delayed rectifying K + channels (Harvey 2001), resulting in increased excitability. In some cases, dendrotoxin converts phasic neurons to tonic (Glazebrook et al 2002;Catacuzzeno et al 2008), indicating that K V 1.1 and K V 1.2 channels are essential to keep phasic neurons phasic. Reduction in the level of dendrotoxin-sensitive K + current is associated with the increase in excitability after nerve damage (Song et al 2012).…”