Noradrenaline contracts arteries by activating voltage-dependent calcium channels.
Noradrenaline (NA) regulates arterial smooth muscle tone and hence blood vessel diameter and blood flow. NA apparently increases tone by causing a calcium influx through the cell membrane. Two calcium influx pathways have been proposed: voltage-activated calcium channels and NA-activated calcium-permeable channels that are voltage-insensitive. Although voltage-activated calcium channels have been identified in arterial smooth muscle, voltage-insensitive calcium channels activated by NA have not. We show here that NA contractions of rabbit mesenteric arteries increase with depolarization. The increase parallels the elevation of open-state probability (P0) of single, voltage-dependent calcium channels. The action of noradrenaline can be explained by NA-activating voltage-dependent calcium channels, rather than by opening a second type of channel. We show directly that NA increases the open-state probability of single calcium channels. Thus, in the presence of NA, calcium entry through voltage-dependent calcium channels can regulate smooth muscle tone at physiological membrane potentials. These results may have relevance to pathophysiological conditions such as hypertension.
Nelson
M T
MT
Department of Pharmacology, University of Vermont College of Medicine, Burlington 05405.
Standen
N B
NB
Brayden
J E
JE
Worley
J F
JF
D000818:Animals; D015220:Calcium Channels / Q000502:physiology*; D008564:Membrane Potentials; D008638:Mesenteric Arteries / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D009638:Norepinephrine / Q000494:pharmacology*; D011817:Rabbits
D015220:Calcium Channels; D009638:Norepinephrine