Calcium-activated potassium currents differentially modulate respiratory rhythm generation.
The pre-Bötzinger complex (PBC) generates eupnea and sighs in normoxia and gasping during hypoxia through particular mixtures of intrinsic and synaptic properties. Among intrinsic properties, little is known about the role of Ca(2+)-activated potassium channels in respiratory rhythms generation. To examine this role, we tested the effects of openers and blockers of the large-conductance (BK) and small-conductance (SK) Ca(2+)-activated potassium channels on the respiratory rhythms recorded both in vitro and in vivo, as well as on the discharge pattern of respiratory neurons in the PBC. Activation of SK channels with 1-ethyl-2-benzimidazolinone (1-EBIO) abolished sigh-like activity and inhibited eupneic-like activity, whereas blockade of SK channels with apamine (APA) increased frequency in both rhythms. In hypoxia, APA did not affect the transition to gasping-like activity. At the cellular level, activation of SK channels abolished pacemaker activity and decreased non-pacemaker neurons discharge; opposite effects were observed with SK blockade. In contrast to SK channel modulation, either activation or blockade of BK channels with NS 1619 or iberiotoxin and paxilline, respectively, produced mild effects on eupneic-like and sigh-like bursts during normoxia in vitro. However, BK blockers prevented the changes associated with the transition to gasping-like activity in vitro and perturbed gasping generation and autoresuscitation in vivo. At the cellular level BK channel modulation did not affect respiratory neurons discharge. We conclude that K(Ca) participate in rhythm generation in a state-dependent manner; SK channels are preferentially involved in rhythm generation in normoxia whereas BK channels participate in the transition to gasping generation in hypoxia.
Zavala-Tecuapetla
C
C
Departamento de Farmacobiología, Centro de Investigación y de Estudios Avanzados del I.P.N., México, DF, México.
Aguileta
M A
MA
Lopez-Guerrero
J J
JJ
González-Marín
M C
MC
Peña
F
F
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn; D001683:Biological Clocks / Q000187:drug effects / Q000502:physiology*; D000860:Hypoxia / Q000378:metabolism / Q000503:physiopathology; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008526:Medulla Oblongata / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D009415:Nerve Net / Q000187:drug effects / Q000378:metabolism; D009434:Neural Pathways / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D010507:Periodicity; D026902:Potassium Channel Blockers / Q000494:pharmacology; D012119:Respiration / Q000187:drug effects*; D012125:Respiratory Center / Q000187:drug effects / Q000378:metabolism*; D051640:Small-Conductance Calcium-Activated Potassium Channels / Q000819:agonists* / Q000037:antagonists & inhibitors; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
D051036:Large-Conductance Calcium-Activated Potassium Channels; D026902:Potassium Channel Blockers; D051640:Small-Conductance Calcium-Activated Potassium Channels