Biophysical properties of Ca2+- and Mg-ATP-activated K+ channels in pulmonary arterial smooth muscle cells isolated from the rat

Abstract

A novel class of Ca(2+)-activated K+ channel, also activated by Mg-ATP, exists in the main pulmonary artery of the rat. In view of the sensitivity of these "KCa,ATP" channels to such charged intermediates it is possible that they may be involved in regulating cellular responses to hypoxia. However, their electrophysiological profile is at present unknown. We have therefore characterised the sensitivity of KCa,ATP channels to voltage, intracellular Ca2+ ([Ca2+]i) and Mg-ATP. They have a conductance of 245 pS in symmetrical K+ and are approximately 20 times more selective for K+ ions than Na+ ions, with a K+ permeability (PK) of 4.6 x 10(-13) cm s-1.Ca2+ ions applied to the intracellular membrane surface of KCa,ATP channels causes a marked enhancement of their activity. This activation is probably the result of simultaneous binding of at least two Ca2+ ions, determined using Hill analysis, to the channel or some closely associated protein. This results in a shift of the voltage activation threshold to more hyperpolarized membrane potentials. The activation of KCa,ATP channels by Mg-ATP has an EC50 of approximately 50 microM. Although the EC50 is unaffected by [Ca2+]i, channel activation by Mg-ATP is enhanced by increasing [Ca2+]i. One possible interpretation of these data is that Mg-ATP increases the sensitivity of KCa,ATP channels to Ca2+. It is therefore possible that under hypoxic conditions, where lower levels of Mg-ATP may be encountered, the sensitivity of KCa,ATP channels to Ca2+ and therefore voltage is reduced.(ABSTRACT TRUNCATED AT 250 WORDS)

Functional characterization of voltage-gated K+ channels in mouse pulmonary artery smooth muscle cells

“…The low dose of TEA (e.g., Յ1 mM) has been demonstrated to be a potent blocker of the large-conductance K Ca channels in vascular smooth muscle cells (32 ] than similar Ca 2ϩ -sensitive K ϩ channels in PASMCs from other species (e.g., humans, rats, rabbits, and dogs) (3,6,8,28,58).…”

“…The "large-conductance" (Ͼ110 pS) current was reminiscent of the intermediate-conductance K Ca current (I K ) but seemed to be different from the large-conductance K Ca current or the MaxiK (or BK) current of ϳ200 pS recorded in rat and human PASMCs (3,25,36,39,60 (Fig. 10, A-C).…”

Relationship between membrane potential, delayed rectifier K+ currents and hypoxia in rat pulmonary arterial myocytes

“…These findings indicated that IK under our recording conditions is primarily due to activation of a delayed rectifier K+ current (IK(V)) with little or no 'K(ca) component, and it is this current which is reduced by hypoxia. Note that the outward current in these cells has been previously characterized in detail (Albarwani et al 1994;Albarwani, Heinert, Turner & Kozlowski, 1995;Salter et al 1995). and pulses to -100 mV, followed by depolarizing pulses (increasing in 10 mV increments to a maximum of +50 mV), were applied under normoxic and hypoxic conditions.…”

General

“…In conclusion, ET-1 activates Iut and I., through a mechanism dependent upon fluctuations in intracellular CaP. (Albarwani et al 1994). It has been speculated that these channels may link cellular metabolism to K+ homeostasis during hypoxia (Albarwani et al 1994).…”

“…(Albarwani et al 1994). It has been speculated that these channels may link cellular metabolism to K+ homeostasis during hypoxia (Albarwani et al 1994). This study was designed to verify whether these ATP-activated Kca channels are specific to pulmonary arterial smooth muscle.…”