# Functional Interactions of Cardiac Ion Channels

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2022 · $634,481

## Abstract

ABSTRACT
 Our laboratory was the first to demonstrate unequivocally that several isoforms of small conductance Ca2+-
activated K+ channels (SK or KCa2 channels) underlie Ca2+-activated K+ current (IK,Ca) in cardiomyocytes. Since
our original reports, knowledge of cardiac SK channels in the field has been greatly expanded. Studies by our
group and more recently by others, have provided evidence to substantiate the important roles of SK channels
in the heart. Interests in cardiac SK channels are further fueled by recent studies suggesting the possible roles
of SK channels in human arrhythmias and atrial fibrillation (AF). Therefore, SK channel may represent a novel
therapeutic target for atrial arrhythmias. Moreover, SK channels are upregulated in heart failure (HF). To our
knowledge, they are the only K+ channels that are upregulated in HF, underpinning the importance of this class
of channels in normal and diseased hearts. Significant gaps in our knowledge and seemingly contradictory
findings on SK channel function in cardiac disease mechanisms are our motivations for the next grant cycle.
These are the challenges: 1) Blockade of SK channels has been shown to be both anti-arrhythmic and
proarrhythmic in various models; and 2) SK channels are upregulated in HF. However, the mechanisms for the
observed upregulation remain incompletely understood. Thus, this multidisciplinary proposal will combine
experimental and computational studies, taking advantage of complementary expertise from four different
laboratories in functional studies, optogenetic tools, and computational modeling to successively address the
multifaceted SK channel remodeling in diseased hearts. SK current is enhanced during -adrenergic (-AR)
stimulation, especially in female animals, therefore, the sex-specific roles of SK channels will be tested. The
proposed study represents the necessary and critical steps to disentangle the highly complex and sex-specific
SK channel remodeling in HF, the unique K+ channel that helps to compensate for the much-needed
“repolarization reserve” in HF.

## Key facts

- **NIH application ID:** 10530871
- **Project number:** 2R01HL085844-13A1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** Nipavan Chiamvimonvat
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $634,481
- **Award type:** 2
- **Project period:** 2007-04-15 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10530871

## Citation

> US National Institutes of Health, RePORTER application 10530871, Functional Interactions of Cardiac Ion Channels (2R01HL085844-13A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10530871. Licensed CC0.

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