Haemoxygenase-2 Theory

Question 1

The possible involvement of HO-2 has been suggested based on ability to convert haem into biliverdin in presence of oxygen producing CO in the process (Kemp, 2005)

Answer 1

antioxidant enzyme constitutively expressed in glomus cells of carotid body

Question 2

It has been proposed that HO-2 mediated production of CO activates K+ channels on the glomus cell membrane

Answer 2

During hypoxic conditions a drop in CO levels leads to K+ channel inhibition

Question 3

Theory proves quite attractive with multiple indications to make HO-2 likely candidate

Answer 3

• HO-2 expressed in rat CB glomus cells
• patch recordings from native BKca channels shown activated by HO-2 substrates

Question 4

Using isolated cat CB

Answer 4

Inhibition of HO-2 with ZnPP-IX mimicked hypoxic conditions whereby carotid sinus nerve activity increased

Question 5

Exogenous addition of CO

Answer 5

reversed HO-2 inhibition by ZnPP-IX indicating the potential role of CO in K+ channel activity

Question 6

Furthermore selective knockdown of HO-2 protein using siRNA

Answer 6

dramatically decreased recombinant human BKca channel activity with exogenous CO administration rescuing this loss of function

Question 7

However as with all theories

Answer 7

HO-2 hypothesis challenged

In vivo studies with HO-2 deficient mice demonstrated unaltered glomus O2 sensitivity compared to WT mice (Ortega Saenz, 2006)