Molecular identification and physiological roles of parotid acinar cell maxi-K channels.
The physiological success of fluid-secreting tissues relies on a regulated interplay between Ca(2+)-activated Cl(-) and K(+) channels. Parotid acinar cells express two types of Ca(2+)-activated K(+) channels: intermediate conductance IK1 channels and maxi-K channels. The IK1 channel is encoded by the K(Ca)3.1 gene, and the K(Ca)1.1 gene is a likely candidate for the maxi-K channel. To confirm the genetic identity of the maxi-K channel and to probe its specific roles, we studied parotid glands in mice with the K(Ca)1.1 gene ablated. Parotid acinar cells from these animals lacked maxi-K channels, confirming their genetic identity. The stimulated parotid gland fluid secretion rate was normal, but the sodium and potassium content of the secreted fluid was altered. In addition, we found that the regulatory volume decrease in acinar cells was substantially impaired in K(Ca)1.1-null animals. We examined fluid secretion from animals with both K(+) channel genes deleted. The secretion rate was severely reduced, and the ion content of the secreted fluid was significantly changed. We measured the membrane potentials of acinar cells from wild-type mice and from animals with either or both K(+) channel genes ablated. They revealed that the observed functional effects on fluid secretion reflected alterations in cell membrane voltage. Our findings show that the maxi-K channels are critical for the regulatory volume decrease in these cells and that they play an important role in the sodium uptake and potassium secretion process in the ducts of these fluid-secreting salivary glands.
Romanenko
Victor
V
Department of Pharmacology and Physiology, University of Rochester Medical Center, New York 14642, USA.
Nakamoto
Tetsuji
T
Srivastava
Alaka
A
Melvin
James E
JE
Begenisich
Ted
T
D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D018118:Chloride Channels / Q000502:physiology; D002712:Chlorides / Q000378:metabolism; D051660:Intermediate-Conductance Calcium-Activated Potassium Channels / Q000235:genetics / Q000502:physiology; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits / Q000235:genetics / Q000502:physiology*; D008564:Membrane Potentials; D051379:Mice; D008810:Mice, Inbred C57BL; D010306:Parotid Gland / Q000378:metabolism*; D011188:Potassium / Q000378:metabolism; D012964:Sodium / Q000378:metabolism
D018118:Chloride Channels; D002712:Chlorides; D051660:Intermediate-Conductance Calcium-Activated Potassium Channels; C465449:Kcnma1 protein, mouse; C496925:Kcnn4 protein, mouse; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; D002217:Carbachol; D012964:Sodium; D011188:Potassium