New Zealand researchers say that calcium-activated potassium ion channels modulate heart rate. The finding, from mice experiments, once better understood, may open the way to pharmacological treatment for hypertension and for heart rate control during surgery.
Heart cell rhythm depends on the opening and closing of a complex series of valves on cell membrane, called ion channels. Thus far it had been thought that calcium-activated potassium (BK) ion channels are not directly involved in heart rate regulation. But now scientists at AgResearch, New Zealand, working with Victoria University and a scientist in the USA, are presenting evidence to the contrary.
They said in PLoS One, "There are a number of K+
channel types expressed in the heart that play key roles in regulating the cardiac cycle. Large conductance calcium-activated potassium (BK) ion channels are not thought to be directly involved in heart function. Here we present evidence that heart rate can be significantly reduced by inhibiting the activity of BK channels."
The researchers made this breakthrough by using mice lacking BK channels (provided by Assistant Prof. Dr Andrea Meredith, now at the University of Maryland School of Medicine) and novel ion channel inhibitory compounds isolated and tested by Drs Dalziel and Finch. Former AgResearch supervised PhD student Wendy Imlach (currently at Columbia University Medical Center) conducted key experiments with Dr Meredith at Stanford University and further investigated the finding in collaboration with Prof. John H. Miller (Victoria University, Wellington). These experiments implicated the heart as being directly involved.
"We're clearly excited by this discovery, and it's fantastic to be involved with something that may pave the way for new heart drugs that act in a completely different way from those currently available. Up until now BK ion channels weren't seen as a factor in modulating heart rate and had been overlooked by scientists" said AgResearch Scientist, Dr Julie Dalziel.
"The results in our study support the hypothesis that BK channels are expressed and functional in the heart. Their tissue location and role in cellular excitability remain to be determined," said Dr Sarah Finch of AgResearch.
The research was funded by a grant from the Marsden Fund, administered by the Royal Society of New Zealand.