Potential role of potassium channel openers in the treatment of asthma and chronic obstructive pulmonary disease.
Airway smooth muscle (ASM) cells express various types of potassium (K+) channels which play a key role in determining the resting membrane potential, a relative electrical stability and the responsiveness to both contractile and relaxant agents. In addition, K+ channels are also involved in modulation of neurotransmitter release from airway nerves. The most important K+ channels identified in airways include large and small Ca2+-activated, delayed-rectifier, and ATP-sensitive channels. These K+ channels are structurally and functionally different, thus playing distinct roles in airway electrophysiology and pharmacology. Many in vitro and in vivo studies, performed in both animals and humans, have shown that K+ channel openers are able to induce hyperpolarization of ASM cells, bronchodilation, suppression of airway hyperresponsiveness (AHR), and inhibition of neural reflexes. Therefore, airway K+ channels represent a suitable pharmacological target for the development of new effective therapeutic options in the treatment of asthma and chronic obstructive pulmonary disease (COPD).
Pelaia
G
G
Department of Pharmacobiological Sciences, University of Catanzaro Magna Graecia, Italy. pelaia@unicz.it
Gallelli
L
L
Vatrella
A
A
Grembiale
R D
RD
Maselli
R
R
De Sarro
G B
GB
Marsico
S A
SA
D000818:Animals; D001249:Asthma / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology*; D006801:Humans; D066298:In Vitro Techniques; D009130:Muscle, Smooth / Q000187:drug effects / Q000503:physiopathology*; D026902:Potassium Channel Blockers / Q000494:pharmacology* / Q000627:therapeutic use; D015221:Potassium Channels / Q000502:physiology*; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology*
D026902:Potassium Channel Blockers; D015221:Potassium Channels