Role of calcium channel blockade in relaxation of tracheal smooth muscle by extracellular Mg2+.
Magnesium ion (Mg2+) is a bronchodilator, but little is known about its mechanism of action on airways. We hypothesized that Mg2+ inhibits voltage-dependent Ca2+ channels of airway smooth muscle. Smooth muscle cells were freshly dispersed from pig trachea with collagenase. Depolarization-induced inward Ca2+ currents, measured in whole cell patch-clamp experiments, were inhibited by nifedipine and stimulated by BAY K 8644. Increasing bath Mg2+ from 1 to 21 mM caused a reversible approximately 30% inhibition of current and a positive shift of the peak current-voltage relationship. Voltage-dependent steady-state inactivation had a half-maximal potential (Vh) of -12 mV and a Boltzmann slope factor (k) of 6.0 mV. High Mg2+ caused a positive shift in Vh without affecting k, whereas nifedipine caused a negative shift in Vh and increased k. The inhibition of voltage-dependent Ca2+ channel currents by Mg2+ was quantitatively similar to Mg(2+)-induced relaxation of KCl-contracted tracheal smooth muscle strips. We conclude that inhibition of Ca2+ influx through dihydropyridine-sensitive, voltage-dependent channels by Mg2+ accounts for much of its relaxant action on airway smooth muscle.
Sonna
L A
LA
Division of Pulmonary and Critical Care Medicine, Johns Hopkins Medical Institutions, Baltimore, Maryland 21205, USA.
Hirshman
C A
CA
Croxton
T L
TL
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism* / Q000502:physiology; D004553:Electric Conductivity; D005110:Extracellular Space / Q000378:metabolism*; D008274:Magnesium / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects / Q000502:physiology*; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology*; D009543:Nifedipine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D013552:Swine; D014132:Trachea / Q000187:drug effects / Q000502:physiology*
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D011189:Potassium Chloride; D008274:Magnesium; D009543:Nifedipine