Nitric oxide induces hyperpolarization by opening ATP-sensitive K(+) channels in guinea pig spiral modiolar artery.
Nitric oxide (NO) hyperpolarizes vascular smooth muscle cells and dilates blood vessels of various beds, but little is known on cochlear vasculatures. Using in vitro preparations of the spiral modiolar artery (SMA), intracellular electrical recording and labeling techniques, we found that the NO donor DPTA-NONOate (10 microM) caused a hyperpolarization of approximately 9 mV in all the cells that had a low resting potential (RP) level near -40 mV. The hyperpolarization amplitude was concentration-dependent, with a 50% effect concentration (EC(50)) of 1 microM. The responses occur in both smooth muscle and endothelial cells, neither of which was blocked by 18beta-glycyrrhetinic acid. The induced hyperpolarization was completely blocked by glipizide, but not by charybdotoxin, apamin, barium, 4-aminopyridine or tetraethylammonium. The hyperpolarizing responses were imitated by pinacidil (EC(50)=30 microM). The pinacidil-induced response was also blocked by glipizide but not by the other K(+) channel blockers mentioned above. Both DPTA-NONOate and pinacidil had little membrane potential effect on cells that had a high RP level near -75 mV. However, when the high RP cells were depolarized to a level beyond -45 mV by barium, both DPTA-NONOate and pinacidil hyperpolarized these cells not differently from those that initially had a low RP. It is concluded that NO hyperpolarizes the SMA primarily by activating K(ATP) channels in both muscle and endothelial cells.
Oregon Hearing Research Center, Oregon Health & Science University, Portland, OR 97201, USA.
Jun-Qiang
JQ
Si
Hui
H
Zhao
Yuqin
Y
Yang
Zhi-Gen
ZG
Jiang
Alfred L
AL
Nuttall
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000475:Alkenes / Q000494:pharmacology; D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000378:metabolism*; D003051:Cochlea / Q000098:blood supply*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D020110:Pinacidil / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*
D000475:Alkenes; D020030:Nitric Oxide Donors; D015221:Potassium Channels; C453079:dipropylenetriamine-NONOate; D009569:Nitric Oxide; D020110:Pinacidil; D000255:Adenosine Triphosphate