Membrane currents in canine bronchial artery and their regulation by excitatory agonists

Abstract

The bronchial vasculature plays an important role in airway physiology and pathophysiology. We investigated the ion currents in canine bronchial smooth muscle cells using patch-clamp techniques. Sustained outward K(+) current evoked by step depolarizations was significantly inhibited by tetraethylamonium (1 and 10 mM) or by charybdotoxin (10(-6) M) but was not significantly affected by 4-aminopyridine (1 or 5 mM), suggesting that it was primarily a Ca(2+)-activated K(+) current. Consistent with this, the K(+) current was markedly increased by raising external Ca(2+) to 4 mM but was decreased by nifedipine (10(-6) M) or by removing external Ca(2+). When K(+) currents were blocked (by Cs(+) in the pipette), step depolarizations evoked transient inward currents with characteristics of L-type Ca(2+) current as follows: 1) activation that was voltage dependent (threshold and maximal at -50 and -10 mV, respectively); 2) inactivation that was time dependent and voltage dependent (voltage causing 50% maximal inactivation of -26 +/- 22 mV); and 3) blockade by nifedipine (10(-6) M). The thromboxane mimetic U-46619 (10(-6) M) caused a marked augmentation of outward K(+) current (as did 10 mM caffeine) lasting only 10-20 s; this was followed by significant suppression of the K(+) current lasting several minutes. Phenylephrine (10(-4) M) also suppressed the K(+) current to a similar degree but did not cause the initial transient augmentation. None of these three agonists elicited inward current of any kind. We conclude that bronchial arterial smooth muscle expresses Ca(2+)-dependent K(+) channels and voltage-dependent Ca(2+) channels and that its excitation does not involve activation of Cl(-) channels.

Mechanical and Electrophysiological Effects of Isoprostanes on Bronchial Arterial Smooth Muscle

“…These findings have been published in full detail elsewhere (Li & Janssen, 2002;Tazzeo et al, 2003).…”

“…For electrophysiological studies of isoprostane responses, porcine bronchial arteries were minced and enzymatically digested (using collagenase and elastase), allowed to settle and adhere to the bottom of a recording chamber (1 ml volume), superfused with standard Ringer's solution at room temperature, and studied using conventional patch-clamp recording techniques (Li & Janssen, 2002).…”

Mechanical and Electrophysiological Effects of Isoprostanes on Bronchial Arterial Smooth Muscle

“…Since ion currents, particularly K + and Ca 2+ currents, play an important role in determining vascular smooth muscle tone, we also examined the electrophysiological actions of isoprostanes. These findings have been published in full detail elsewhere (Li & Janssen, 2002;Tazzeo et al, 2003).…”

Thromboxane A 2 -Induced Inhibition of Voltage-Gated K + Channels and Pulmonary Vasoconstriction

“…14,[22][23][24] Very little is known about the effects of TXA 2 on vascular K ϩ channels. It has been reported that TXA 2 analogues inhibit the activity of BK Ca channels in bronchial and coronary arteries, 25,26 whereas their effects on vascular K V channels are unknown. We hypothesized that TXA 2 might inhibit K V channels, thereby establishing a link between these two pathogenic pathways in pulmonary hypertension.…”