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Hypoxia activates chemoreceptor cells of the carotid body (CB) promoting an increase in their normoxic release of neurotransmitters. Catecholamine (CA) release rate parallels the intensity of hypoxia. Coupling of hypoxia to CA release requires cell depolarization, produced by inhibition of [O.sub.2]-regulated [K.sup.+] channels, and [Ca.sup.2+] entering the cells via voltage-operated channels. In rat chemoreceptor cells hypoxia inhibits large-conductance, calcium-sensitive K channels (maxiK) and a two-pore domain weakly inward rectifying [K.sup.+] channel (TWIK)-like acid-sensitive [K.sup.+] channel (TASK)-like channel, but the significance of maxiK is controversial. A proposal envisions maxiK contributing to set the membrane potential ([E.sub.m]) and the hypoxic response, but the proposal is denied by authors finding that maxiK inhibition does not depolarize chemoreceptor cells or alters intracellular [Ca.sup.2+] concentration or CA release in normoxia or hypoxia. We found that maxiK channel blockers (tetraethylammonium and iberiotoxin) did not modify CA release in rat chemoreceptor cells, in either normoxia or hypoxia, and iberiotoxin did not alter the [Ca.sup.2+] transients elicited by hypoxia. On the contrary, both maxiK blockers increased the responses elicited by dinitrophenol, a stimulus we demonstrate does not affect maxiK channels in isolated patches of rat chemoreceptor cells. We conclude that in rat chemoreceptor cells maxiK channels do not contribute to the genesis of the [E.sub.m], and that their full inhibition by hypoxia, preclude further inhibition by maxiK channel blockers. We suggest that full inhibition of this channel is required to generate the spiking behavior of the cells in acute hypoxia. hypoxia; catecholamine; iberiotoxin; intracellular calcium

In this work we have combined biochemical and electrophysiological approaches to explore the modulation of rat ventricular transient outward [K.sup.+] current ([I.sub.tO]) by calmodulin kinase II (CaMKII). Intracellular application of CaMKII inhibitors KN93, calmidazolium, and autocamtide-2-related inhibitory peptide II (ARIP-II) accelerated the inactivation of [I.sub.tO], even at low [[Ca.sup.2+]]. In the same conditions, CaMKII coimmunoprecipitated with Kv4.3 channels, suggesting that phosphorylation of Kv4.3 channels modulate inactivation of [I.sub.tO]. Because channels underlying [I.sub.tO] are heteromultimers of Kv4.2 and Kv4.3, we have explored the effect of CaMKII on human embryonic kidney (HEK) cells transfected with either of those Kv[alpha]-subunits. Whereas Kv4.3 inactivated faster upon inhibition of CaMKII, Kv4.2 inactivation was insensitive to CaMKII inhibitors. However, Kv4.2 inactivation became slower when high [Ca.sup.2+] was used in the pipette or when intracellular [[Ca.sup.2+]] ([[Ca.sup.2+]]i) was transiently increased. This effect was inhibited by KN93, and Western blot analysis demonstrated [Ca.sup.2+]-dependent phosphorylation of Kv4.2 channels. On the contrary, CaMKII coimmunoprecipitated with Kv4.3 channels without a previous [Ca.sup.2+] increase, and the association was inhibited by KN93. These results suggest that both channels underlying [I.sub.tO] are substrates of CaMKII, although with different sensitivities; Kv4.2 remain unphosphorylated unless [[Ca.sup.2+]]i increases, whereas Kv4.3 are phosphorylated at rest. In addition to the functional impact that phosphorylation of Kv4 channels could cause on the shape of action potential, association of CaMKII with Kv4.3 provides a new role of Kv4.3 subunits as molecular scaffolds for concentrating CaMKII in the membrane, allowing [Ca.sup.2+]-dependent modulation by this enzyme of the associated Kv4.2 channels. transient outward current; cardiac electrophysiology; immunoprecipitation

A study was conducted to analyze the effects of Kv-beta-1.2 coexpression on the characteristics of shaker and Kv4.2 voltage-gated K+ channel alpha subunits in transfected HEK293 cells. Results indicated that Kv-beta-1.2 functionally associates with two alpha subunits to modulate various characteristics of the heteromultimers. Findings also showed that it accelerates the rate of inactivation of the Shaker currents.

Presents information on a study on the association of the auxiliary subunit Kv...1.2. with some cloned voltage-gated potassium channels and its possible contribution to the hypoxic sensitivity of the heteromultimers. Materials and methods; Results and discussion.