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X Zhan
H Asmara
G Sahu
J Miclat
C Szalay

Hadhimulya Asmara Postdoctoral Fellow    
BSc Biology, Univ. Indonesia 2001
MSc Biomedicine Univ. Indonesia 2005
PhD Univ. Kagoshima, Japan 2010
PhD Dissertation: Calmodulin interactions with Cav1.2 calcium channels

Hotchkiss Brain Institute
Health Research Innovation Center (HRIC) 1B42A
University of Calgary
Calgary Alberta Canada
T2N 4N1
Phone: 403-220-8451
FAX: 403-210-7446

PhD Molecular Biology & Neurocardio-vascular Research
Univ. Kagoshima
Supervisor: Professor M. Kameyama, MD, PhD

2010 -
University of Calgary
Calgary Alberta
Supervisors: Dr. R.W. Turner, G Zamponi
Scholarship Ministry of Education, Indonesia, 2001-2005.


Scholarship Ministry of Education, Japan, 2005-2010

Research Focus: Calmodulin interactions in cerebellum
Approach: Molecular biology, electrophysiology in vitro, pharmacology
Preparations: Expression systems, in vitro slice preparations
Below are short summaries of my publications.

PhD Thesis research:
My PhD work centered on the interaction sites between calmodulin and L-type (Cav1.2) calcium channels

CaMod binding to mutated preIQ and IQ peptides Multiple Calmodulin binding sites on Cav1.2
In this study, we examined the interaction between calmodulin and the Cav1.2 calcium channel using a semi-quantitative pull-down assay. We found that the C terminus of Cav1.2 calcium channels can simultaneously bind two molecules of calmodulin to modulate its facilitatory and inhibitory activities. PDF
Model of CaM interactions with Cav1.2 Role of N- and C-lobes of Calmodulin in regulation of Cav1.2
In this work, we examined the effects of CaM mutants on calcium-dependent regulation of cardiomyocyte Cav1.2 calcium channels using inside-out patch recordings. CaM mutants designed to interfere with calcium binding to either the N- or C-lobes of CaM revealed that both lobes are necessary for producing a calcium-dependent leftward shift in the concentration response curve of Cav1.2 calcium channels. PDF
Model of CaM interactions with Cav1.2 Calpastatin domain L is a partial agonist of the Cav1.2 CaMod binding site
In this study we compared the effects of Calpastatin (CSL) with those of calmodulin (CaM) on Cav1.2 channels, and investigated the functional relationship between CSL and CaM in guinea-pig ventricular myocytes. Using inside-out recordings we found that CSL regulates channel activity in a manner consistent with a partial agonist of CaM, and that the binding site locates in the IQ region of the C-terminal tail of the Cav1.2 channel. PDF

Postdoctoral research:
My work is focused on the interaction between calcium channel isoforms and calcium sensor proteins involved in modulating potassium channels.

Charybdotoxin slows the rate or repolarization of the parallel fiber-evoked EPSP An intermediate conductance KCa channel modifies parallel fiber EPSPs in Purkinje cells
   Purkinje cells were known to express the two KCa channels typically found in central neurons (SK and BK channels). This study reports that the intermediate conductance KCa channel (KCa3.1) is also expressed in Purkinje cells and is linked to Cav3.2 T-type calcium channels. KCa3.1 is activated during the parallel fiber EPSP to increase the EPSP rate of decay and generate a long duration AHP to suppress temporal summation of low frequency EPSPs, allowing Purkinje cells to respond to sensory-like bursts of parallel fiber input. See Engbers et al. (2012).
IKCa channels are a major determinant of the CA1 hippocampal pyramidal cell sAHP IKCa channels are a critical determinant of the CA1 pyramidal cell slow AHP
   CA1 pyramidal cells have been shown to express immunolabel and promoter activity of the IKCa channel. Recordings of the slow AHP in CA1 pyramidal cells revealed single channels that match the pharmacological profile of IKCa channels, which prove to underlie the long duration slow AHP. Block of IKCa channels confirm a key role in reducing temporal summation of EPSPs and mediating spike accommodation. (see King et al. (2015)).

Peer-Reviewed Publications

Asmara, H. (2004) The effect of HIV virus on male reproduction system. Medica Islamica 1:10-15.

Asmara, H.,
Minobe, E., Saud, Z.A., Kameyma, M. (2010a) Interactions of calmodulin with the multiple binding sites of Cav1.2 calcium channels. J Pharmac Sci (JPS) 112(4):397-404. PDF

Guo, F., Minobe, E., Yazawa, K., Asmara, H., Bai, X.-Y., Han, D.-Y., Hao, L.-Y. and Kameyama, M. (2010b) Both N- and C-lobes of calmodulin are required for calcium-dependent regulation of Cav1.2 calcium channels. Biochem Biophys Res Comm 391: 1170-1176. PDF

Minobe, E., Asmara, H., Saud, Z.A. and Kameyama, M. (2011) Calpastatin domain L is a partial agonist of the calmodulin-binding site for channel activation in Cav1.2 calcium channels. J. Biol. Chem. eprint, Sept. 21. PDF

Engbers, J.D.T.*, Anderson, D.*, Asmara, H., Rehak, R., Mehaffey, W.H., Hameed, S., McKay, B.E., Kruskic, M., Zamponi, G.W. and Turner, R.W. (2012) Intermediate conductance calcium-activated potassium channels modulate summation of parallel fiber input in cerebellar Purkinje cells. PNAS 109 (7): 2601-2606. * Shared first authors. Faculty of 1000 citation. PDF

King, B.*, Rizwan, A.P.*, Asmara, H., Heath, N.C., Engbers, J.D.T, Dykstra, J., Bartoletti, T.M., Hameed, S., Zamponi, G.W., and Turner, R.W.(2015) IKCa channels are a critical determinant of the slow AHP in CA1 pyramidal neurons. * Shared first authors. Cell Reports. 11:1-8. Link

Turner, R.W., Asmara, H., Engbers, J.D.T., Miclat, J., Rizwan, A.P., Sahu, G., and Zamponi, G.W. (2016) Assessing the role of IKCa channels in generating the slow AHP of CA1 hippocampal pyramidal cells. Channels. 10(4): 313-319. Link

Asmara, H., Ileana M., Rizwan, A.P., Sahu, G., Simms, B.A., Zhang, F-X, Engbers, J.D.T., Stys, P.K., Zamponi, G.W., and Turner, R.W. (2017) A T-type channel-calmodulin complex triggers alpha-CaMKII activation, Molecular Brain, 10:37. PDF.

Sahu, G., Asmara, H., Zhang, F-X, Zamponi, G.W. and Turner, R.W. (2017) Activity-dependent facilitation of CaV1.3 calcium channels promotes KCa3.1 activation in hippocampal neurons. J. Neuroscience. 37(46):11255-11270. PDF

Key Abstracts

Asmara, H, Minobe E, Saud E, Wang WY, Kameyama M. Interactions of N- and C-lobes of calmodulin with the C-terminal tail of Cav1.2 calcium channel. J. Physio.l Sci. 58: S72, 2008.

Asmara H, Minobe E, Saud ZA, Wang WY, Kameyama M. Multiple binding sites of calmodulin in the C-terminal tail of Cav1.2 calcium channel. J. Physiol. Sci. 59: S251, 2009.

Asmara H, Minobe E, Saud ZA, Kameyama M. Multiple molecules of calmodulin bind to the Cav1.2 calcium channel. Journal of Physiol. Soc. Japan 72: 46, 2010.

King, B., Teves, M., Seredynski, T., Kruskic, M., Asmara, H., Engbers, J.D.T., Hameed, S., Zamponi, G.W. and Turner, R.W. Expression pattern of the intermediate conductance Ca-activated K channel in the CNS. Can. Assoc. Neurosci., 2013.

Asmara, H., Bartoletti, T.M., Rehak, R., Micu, I., Hameed, S., Stys, P., Zamponi, G.W. and Turner, R.W. A novel complex between T-type calcium channels and calmodulin. Can. Assoc. Neurosci., 2013.

King, B., Teves, M., Kruskic, M., Asmara, H., Engbers, J.D.T., Hameed, S., Zamponi, G.W. and Turner, R.W.  Widespread expression of the intermediate conductance calcium-activated potassium channel in central neurons.  Gordon Conference, Cerebellum, 2013.

Asmara, H., Heath N.C., Simms, B., Bartoletti, T.M., Rehak, R., Micu, I., Zhang, F.X., Stys, P., Zamponi, G.W. and Turner, R.W. T-type calcium channels form a calcium-dependent complex with calmodulin. Proc. Soc. Neurosci., 2014.

King, B.*, Rizwan, A.P.*, Heath, N.C., Asmara, H., Dykstra, S., Zamponi, G.W. and Turner, R.W.  IKCa channels are a critical determinant of the slow AHP in hippocampus.  Can. Assoc. Neurosci., 2015.

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